Pub Date : 2026-01-27DOI: 10.1016/j.adcanc.2026.100173
Saghar Yousefnia
Cancer stem cells (CSCs) are a small population of cancerous cells with aggressive phenotypes. Exosomes are small vesicles derived from cancer cells and CSCs containing non-coding RNAs, exhibiting tumor-promoting activity. Non-coding RNAs play a crucial role in tumor progression and metastasis, offering new insights into the complex mechanisms of cancer development. By transferring non-coding RNAs between cells, exosomes modulate gene expression and signaling pathways, ultimately affecting cancer cell behaviors such as proliferation, migration, invasion and therapy resistance. This review summarizes the tumor-promoting activity of CSCs-derived exosomal non-coding RNAs (miRNA/lncRNAs/circRNAs) in different types of cancer cells. Elucidating the intricate cross-talk between exosomal non-coding RNAs, CSCs and tumor cells has the potential to develop a new approach to target these types of cancer cells. This review highlights the therapeutic potential of targeting CSC-derived exosomal ncRNAs to develop more effective strategies for aggressive cancers.
{"title":"The roles of cancer stem cell (CSC)-derived exosomal non-coding RNAs in cancer progression","authors":"Saghar Yousefnia","doi":"10.1016/j.adcanc.2026.100173","DOIUrl":"10.1016/j.adcanc.2026.100173","url":null,"abstract":"<div><div>Cancer stem cells (CSCs) are a small population of cancerous cells with aggressive phenotypes. Exosomes are small vesicles derived from cancer cells and CSCs containing non-coding RNAs, exhibiting tumor-promoting activity. Non-coding RNAs play a crucial role in tumor progression and metastasis, offering new insights into the complex mechanisms of cancer development. By transferring non-coding RNAs between cells, exosomes modulate gene expression and signaling pathways, ultimately affecting cancer cell behaviors such as proliferation, migration, invasion and therapy resistance. This review summarizes the tumor-promoting activity of CSCs-derived exosomal non-coding RNAs (miRNA/lncRNAs/circRNAs) in different types of cancer cells. Elucidating the intricate cross-talk between exosomal non-coding RNAs, CSCs and tumor cells has the potential to develop a new approach to target these types of cancer cells. This review highlights the therapeutic potential of targeting CSC-derived exosomal ncRNAs to develop more effective strategies for aggressive cancers.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"16 ","pages":"Article 100173"},"PeriodicalIF":3.0,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146077523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-24DOI: 10.1016/j.adcanc.2026.100172
Olesya S. Malyarenko , Anna O. Kravchenko , Valery R. Druzhinina , Rohit Gundamaraju , Svetlana P. Ermakova , Ranga Rao Ambati
Epithelial-mesenchymal transition (EMT) represents a process whereby an epithelial cell undergoes a series of alterations, acquiring the morphological and functional characteristics of a mesenchymal cell. EMT plays a significant role in the progression of cancerous cells, including metastasis, tumor heterogeneity and drug resistance. Despite the identification of multiple molecular pathways implicated in the regulation of tumor EMT, no specific treatment has been developed to target this process. The bioactive compounds derived from seaweeds represent a significant area of research interest, given their potential therapeutic applications in a range of diseases. Sulfated glycans, derived from brown, red, and green algae, as well as their derivatives, have demonstrated anticancer activity in vitro, in vivo, and under preclinical conditions. This review summarizes the key and pivotal aspects of the use of fucoidans, carrageenans, and ulvans derived from brown, red, and green algae, respectively, and their derivatives, in the modulation of pathological EMT or its deleterious effects through the modulation of various cellular signal transduction pathways, both in vitro and in vivo. The objective of this review is to elucidate the molecular mechanisms underlying the antitumor effects of sulfated seaweed's glycans and to provide insights into the relevance of individual polysaccharides in influencing tumor EMT, which may contribute to the development of new alternative cancer treatment options.
{"title":"Targeting epithelial-to-mesenchymal transition of cancer cells by sulfated glycans from marine algae","authors":"Olesya S. Malyarenko , Anna O. Kravchenko , Valery R. Druzhinina , Rohit Gundamaraju , Svetlana P. Ermakova , Ranga Rao Ambati","doi":"10.1016/j.adcanc.2026.100172","DOIUrl":"10.1016/j.adcanc.2026.100172","url":null,"abstract":"<div><div>Epithelial-mesenchymal transition (EMT) represents a process whereby an epithelial cell undergoes a series of alterations, acquiring the morphological and functional characteristics of a mesenchymal cell. EMT plays a significant role in the progression of cancerous cells, including metastasis, tumor heterogeneity and drug resistance. Despite the identification of multiple molecular pathways implicated in the regulation of tumor EMT, no specific treatment has been developed to target this process. The bioactive compounds derived from seaweeds represent a significant area of research interest, given their potential therapeutic applications in a range of diseases. Sulfated glycans, derived from brown, red, and green algae, as well as their derivatives, have demonstrated anticancer activity <em>in vitro</em>, <em>in vivo</em>, and under preclinical conditions. This review summarizes the key and pivotal aspects of the use of fucoidans, carrageenans, and ulvans derived from brown, red, and green algae, respectively, and their derivatives, in the modulation of pathological EMT or its deleterious effects through the modulation of various cellular signal transduction pathways, both <em>in vitro</em> and <em>in vivo</em>. The objective of this review is to elucidate the molecular mechanisms underlying the antitumor effects of sulfated seaweed's glycans and to provide insights into the relevance of individual polysaccharides in influencing tumor EMT, which may contribute to the development of new alternative cancer treatment options.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"16 ","pages":"Article 100172"},"PeriodicalIF":3.0,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146077522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-13DOI: 10.1016/j.adcanc.2026.100170
Xuxia Ye , Fanfan Yang , Hui Huang , Mengli Wu , Jin Chen , Bin Xu , Jian Xu
Gastric cancer (GC) is a common gastrointestinal malignancy, with more than one million new cases diagnosed each year. Identifying biomarkers for early diagnosis and prognosis is crucial to improving clinical outcomes. However, existing biomarkers lack sufficient sensitivity and specificity. Gamma-glutamyltransferases (GGTs) are a family of enzymes involved in glutathione metabolism and cancer progression, and recent studies have suggested their potential as tumor markers. Among them, GGT5 (Gamma-glutamyltransferase 5) has been reported to play oncogenic roles in gastrointestinal cancers.This study aims to explore the regulatory relationship between miRNA-4722-3p and GGT5 and its impact on GC progression, evaluating the potential of miRNA-4722-3p as a diagnostic biomarker for GC. Bioinformatics tools, including TargetScan, miRWalk, and miRDB, were used to predict miRNAs that bind to the 3’ untranslated region (UTR) of GGT5. miRNA-4722-3p was selected due to its lowest binding free energy and was validated through dual-luciferase reporter assays. RT-qPCR and Western blotting confirmed that miRNA-4722-3p directly targets and inhibits GGT5 expression in GC cells. Functional assays demonstrated that miRNA-4722-3p upregulation significantly suppressed GC cell proliferation and migration, whereas its downregulation enhanced these processes. Furthermore, miRNA-4722-3p inhibited GGT5 expression through the PI3K/AKT-MAPK-MMPs signaling pathway, reinforcing its suppressive effects. Overall, miRNA-4722-3p and GGT5 may serve as promising biomarkers for the early diagnosis and targeted therapy of gastric cancer.
Summary
Bioinformatics and experiments identify miR-4722-3p as a gastric cancer biomarker. It suppresses tumor growth/metastasis by targeting oncogene GGT5 and inhibiting the PI3K/AKT-MAPK-MMPs pathway, revealing its tumor-suppressive role and offering a novel therapeutic target.
{"title":"miRNA-4722-3p targets GGT5 and inhibits gastric cancer cell progression via the PI3K/AKT-MAPK-MMPs signaling pathway","authors":"Xuxia Ye , Fanfan Yang , Hui Huang , Mengli Wu , Jin Chen , Bin Xu , Jian Xu","doi":"10.1016/j.adcanc.2026.100170","DOIUrl":"10.1016/j.adcanc.2026.100170","url":null,"abstract":"<div><div>Gastric cancer (GC) is a common gastrointestinal malignancy, with more than one million new cases diagnosed each year. Identifying biomarkers for early diagnosis and prognosis is crucial to improving clinical outcomes. However, existing biomarkers lack sufficient sensitivity and specificity. Gamma-glutamyltransferases (GGTs) are a family of enzymes involved in glutathione metabolism and cancer progression, and recent studies have suggested their potential as tumor markers. Among them, GGT5 (Gamma-glutamyltransferase 5) has been reported to play oncogenic roles in gastrointestinal cancers.This study aims to explore the regulatory relationship between miRNA-4722-3p and GGT5 and its impact on GC progression, evaluating the potential of miRNA-4722-3p as a diagnostic biomarker for GC. Bioinformatics tools, including TargetScan, miRWalk, and miRDB, were used to predict miRNAs that bind to the 3’ untranslated region (UTR) of GGT5. miRNA-4722-3p was selected due to its lowest binding free energy and was validated through dual-luciferase reporter assays. RT-qPCR and Western blotting confirmed that miRNA-4722-3p directly targets and inhibits GGT5 expression in GC cells. Functional assays demonstrated that miRNA-4722-3p upregulation significantly suppressed GC cell proliferation and migration, whereas its downregulation enhanced these processes. Furthermore, miRNA-4722-3p inhibited GGT5 expression through the PI3K/AKT-MAPK-MMPs signaling pathway, reinforcing its suppressive effects. Overall, miRNA-4722-3p and GGT5 may serve as promising biomarkers for the early diagnosis and targeted therapy of gastric cancer.</div></div><div><h3>Summary</h3><div>Bioinformatics and experiments identify miR-4722-3p as a gastric cancer biomarker. It suppresses tumor growth/metastasis by targeting oncogene GGT5 and inhibiting the PI3K/AKT-MAPK-MMPs pathway, revealing its tumor-suppressive role and offering a novel therapeutic target.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"16 ","pages":"Article 100170"},"PeriodicalIF":3.0,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146022507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-12DOI: 10.1016/j.adcanc.2026.100171
Biaogang Han , Juan Li , Li Li , Yongqing Shen , Xiaoqiang Guo , Aixia Sui
Purpose
This study investigated the pharmacological effects and potential mechanisms of the tyrosine kinase inhibitor anlotinib and the histone lysine demethylase 6 B (KDM6B) inhibitor GSK-J4 on glioma cells.
Methods
Brain pathological samples were analyzed with immunohistochemistry. The glioma cells U87MG and U251, and brain endothelial cell hCMEC/D3 were used in this study. Cell proliferation and migration were determined with CCK8 and scratch assays. The mRNA expressions of platelet derived growth factor receptor alpha (PDGFRA), PDGFR beta (PDGFRB) and KDM6B were detected with RT-qPCR. The protein levels of total PDGFRA and phosphorylated PDGFRA (p-PDGFRA) were measured with western blotting.
Results
The protein levels of total PDGFRA, p-PDGFRA and KDM6B were significantly elevated in malignant glioma tissues relative to control brain tissues. In vitro experiments demonstrated that anlotinib effectively inhibited glioma cell proliferation and migration, while GSK-J4 increased its inhibitory activity. The combination of two inhibitors showed no additional cytotoxicity toward brain endothelial cells. Further studies elucidated that the anlotinib primarily functions as a PDGFRA kinase inhibitor, whereas GSK-J4 exerts its effects through transcriptional repression of PDGFRA gene expression.
Conclusion
The combination of anlotinib and GSK-J4 achieves dual inhibition of PDGFRA at both transcriptional and post-translational levels, representing a promising therapeutic strategy for glioma patients.
{"title":"Histone demethylase KDM6B inhibitor GSK-J4 sensitizes glioma cells to tyrosine kinase inhibitor anlotinib in vitro by reducing PDGFRA expression","authors":"Biaogang Han , Juan Li , Li Li , Yongqing Shen , Xiaoqiang Guo , Aixia Sui","doi":"10.1016/j.adcanc.2026.100171","DOIUrl":"10.1016/j.adcanc.2026.100171","url":null,"abstract":"<div><h3>Purpose</h3><div>This study investigated the pharmacological effects and potential mechanisms of the tyrosine kinase inhibitor anlotinib and the histone lysine demethylase 6 B (KDM6B) inhibitor GSK-J4 on glioma cells.</div></div><div><h3>Methods</h3><div>Brain pathological samples were analyzed with immunohistochemistry. The glioma cells U87MG and U251, and brain endothelial cell hCMEC/D3 were used in this study. Cell proliferation and migration were determined with CCK8 and scratch assays. The mRNA expressions of platelet derived growth factor receptor alpha (<em>PDGFRA</em>), PDGFR beta (<em>PDGFRB</em>) and <em>KDM6B</em> were detected with RT-qPCR. The protein levels of total PDGFRA and phosphorylated PDGFRA (p-PDGFRA) were measured with western blotting.</div></div><div><h3>Results</h3><div>The protein levels of total PDGFRA, p-PDGFRA and KDM6B were significantly elevated in malignant glioma tissues relative to control brain tissues. <em>In vitro</em> experiments demonstrated that anlotinib effectively inhibited glioma cell proliferation and migration, while GSK-J4 increased its inhibitory activity. The combination of two inhibitors showed no additional cytotoxicity toward brain endothelial cells. Further studies elucidated that the anlotinib primarily functions as a PDGFRA kinase inhibitor, whereas GSK-J4 exerts its effects through transcriptional repression of <em>PDGFRA</em> gene expression.</div></div><div><h3>Conclusion</h3><div>The combination of anlotinib and GSK-J4 achieves dual inhibition of PDGFRA at both transcriptional and post-translational levels, representing a promising therapeutic strategy for glioma patients.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"16 ","pages":"Article 100171"},"PeriodicalIF":3.0,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145976551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-30DOI: 10.1016/j.adcanc.2025.100169
Easwari Kumaraswamy , Raeann M. Koren Shimak , Sumedha Gunewardena , Dani Alexander , Karen L. Wendt , Stacey L. Hembruff , Roy A. Jensen
BRCA1-associated basal-like breast cancers (BLBCs) are high-grade ductal carcinomas that frequently overexpress epidermal growth factor receptor (EGFR). EGFR overexpression is associated with tumor progression and metastasis, resistance to radiation and chemotherapy, and poor prognosis. Though EGFR inhibitors have been used to treat other cancers, clinical trials for breast cancer have been unsuccessful due to poor response rates. Previous study showed that BRCA1 exerts regulatory control over dozens of important miRNAs that play a critical role in breast neoplasia. In addition, it established that BRCA1 regulates EGFR expression via miR-146a and provided a rationale for the development of miR-146a based therapeutic strategies. The current study further investigates the role of BRCA1 and miR-146a in regulating EGFR signaling. Analysis of The Cancer Genome Atlas (TCGA) data reveals that low expression of miR-146a is associated with distinctively poor overall survival of TNBC patients. miR-146a loss/gain of function experiments in vitro demonstrates that BRCA1 and miR-146a regulate EGFR signaling, extracellular matrix (ECM) remodeling and chemoresistance. Using in vivo mouse models, the study further shows that miR-146a overexpression delays tumor formation leading to better overall survival. Since one miRNA can target multiple genes and regulate multiple signaling pathways, this study provides evidence to suggest that restoring miR-146a could suppress EGFR signaling and other compensatory pathways, providing a targeted therapeutic option for BRCA1 associated BLBC.
{"title":"microRNA 146a suppresses tumor progression and enhances therapeutic sensitivity by targeting the EGFR pathway in BRCA1-associated basal-like breast cancers","authors":"Easwari Kumaraswamy , Raeann M. Koren Shimak , Sumedha Gunewardena , Dani Alexander , Karen L. Wendt , Stacey L. Hembruff , Roy A. Jensen","doi":"10.1016/j.adcanc.2025.100169","DOIUrl":"10.1016/j.adcanc.2025.100169","url":null,"abstract":"<div><div>BRCA1-associated basal-like breast cancers (BLBCs) are high-grade ductal carcinomas that frequently overexpress epidermal growth factor receptor (EGFR). EGFR overexpression is associated with tumor progression and metastasis, resistance to radiation and chemotherapy, and poor prognosis. Though EGFR inhibitors have been used to treat other cancers, clinical trials for breast cancer have been unsuccessful due to poor response rates. Previous study showed that BRCA1 exerts regulatory control over dozens of important miRNAs that play a critical role in breast neoplasia. In addition, it established that BRCA1 regulates EGFR expression via miR-146a and provided a rationale for the development of miR-146a based therapeutic strategies. The current study further investigates the role of BRCA1 and miR-146a in regulating EGFR signaling. Analysis of The Cancer Genome Atlas (TCGA) data reveals that low expression of miR-146a is associated with distinctively poor overall survival of TNBC patients. miR-146a loss/gain of function experiments <em>in vitro</em> demonstrates that BRCA1 and miR-146a regulate EGFR signaling, extracellular matrix (ECM) remodeling and chemoresistance. Using <em>in vivo</em> mouse models, the study further shows that miR-146a overexpression delays tumor formation leading to better overall survival. Since one miRNA can target multiple genes and regulate multiple signaling pathways, this study provides evidence to suggest that restoring miR-146a could suppress EGFR signaling and other compensatory pathways, providing a targeted therapeutic option for BRCA1 associated BLBC.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"16 ","pages":"Article 100169"},"PeriodicalIF":3.0,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145925274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-23DOI: 10.1016/j.adcanc.2025.100168
Zohreh Amiri , Mehdi Forouzandeh Moghadam , Zahra Sadat Hashemi , Majid Sadeghizadeh , Abdolah Razi
Introductio
n: Salinomycin (SAL) and doxorubicin (DOX) have previously garnered much attention as anticancer drugs. However, their encapsulation within a nanocarrier dendrosome and their possible synergistic effect have not been reported, which we aim to address.
Methods
SAL and DOX were loaded into the produced OA400 nanocarrier. Then, their effects on cell viability, apoptosis, migration, and invasion were analyzed in MDA-MB-231 and MCF-7 cells. The evaluations were conducted using MTT, flow cytometry, scratch, and Matrigel tests. The treatments were performed with encapsulated and free forms of the individual drugs, and in combination. The miRNAs Let-7, miR-21, miR-10b, and miR-128 expression was assessed by qRT-PCR to evaluate the cellular effects of the treatments.
Results
The results showed that the combination of free SAL and DOX and the combination of SAL and DOX loaded in OA400 were more effective than their treatment as singular drugs in the inhibition of proliferation and induction of apoptosis. The expression of miRNAs, miR-21 and miR-10b, the most important tumor miRNAs, was decreased, and the expression of Let-7, an inhibitor of tumor growth, was increased. However, miR-128 expression didn't change significantly.
Conclusion
The nanocarrier OA400 provides a potential strategy for targeted delivery of SAL and DOX, providing a sustained release profile. Moreover, combined administration of these drugs showed a synergistic anticancer activity, which could be deemed as an effective anti-cancer therapy against breast cancer. Despite the obtained promising results, further in vivo studies would shed light on the true potential of this strategy.
{"title":"Anti-breast cancer effects of free and nanocarrier-loaded salinomycin and doxorubicin","authors":"Zohreh Amiri , Mehdi Forouzandeh Moghadam , Zahra Sadat Hashemi , Majid Sadeghizadeh , Abdolah Razi","doi":"10.1016/j.adcanc.2025.100168","DOIUrl":"10.1016/j.adcanc.2025.100168","url":null,"abstract":"<div><h3>Introductio</h3><div>n: Salinomycin (SAL) and doxorubicin (DOX) have previously garnered much attention as anticancer drugs. However, their encapsulation within a nanocarrier dendrosome and their possible synergistic effect have not been reported, which we aim to address.</div></div><div><h3>Methods</h3><div>SAL and DOX were loaded into the produced OA400 nanocarrier. Then, their effects on cell viability, apoptosis, migration, and invasion were analyzed in MDA-MB-231 and MCF-7 cells. The evaluations were conducted using MTT, flow cytometry, scratch, and Matrigel tests. The treatments were performed with encapsulated and free forms of the individual drugs, and in combination. The miRNAs Let-7, miR-21, miR-10b, and miR-128 expression was assessed by qRT-PCR to evaluate the cellular effects of the treatments.</div></div><div><h3>Results</h3><div>The results showed that the combination of free SAL and DOX and the combination of SAL and DOX loaded in OA400 were more effective than their treatment as singular drugs in the inhibition of proliferation and induction of apoptosis. The expression of miRNAs, miR-21 and miR-10b, the most important tumor miRNAs, was decreased, and the expression of Let-7, an inhibitor of tumor growth, was increased. However, miR-128 expression didn't change significantly.</div></div><div><h3>Conclusion</h3><div>The nanocarrier OA400 provides a potential strategy for targeted delivery of SAL and DOX, providing a sustained release profile. Moreover, combined administration of these drugs showed a synergistic anticancer activity, which could be deemed as an effective anti-cancer therapy against breast cancer. Despite the obtained promising results, further <em>in vivo</em> studies would shed light on the true potential of this strategy.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"16 ","pages":"Article 100168"},"PeriodicalIF":3.0,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146077582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Epithelial–mesenchymal transition (EMT) plays a dual role in driving both metastatic progression and therapy resistance in colorectal cancer (CRC). To identify systemic EMT-related signals across disease stages, we performed stage-specific plasma proteomics in treatment-naïve CRC patients from an Asia–Pacific (APAC)-representative discovery cohort in India. EMT-associated proteins were curated using FANTOM5 and validated through MSigDB enrichment, with protein interaction networks constructed via STRING and GeneMANIA. We developed an EMT Progression and Resistance Index (EPRI) that integrates literature support, stage specificity, and clinical trial relevance to prioritize clinically meaningful effectors. EPRI identified NAMPT as a central hub enriched in Stage I plasma, consistent with metabolic priming via NAD+ biosynthesis. A NAMPT-centered subnetwork revealed stage-dependent interactions spanning complement and metabolic pathways, implicating systemic redox remodeling and PI3K/Akt signaling in EMT-driven dissemination and 5-FU/FOLFOX resistance. In later stages (III–IV), plasma signatures consolidated into complement pathway activation (notably elevated C4A/B and CR1), reflecting immune remodeling and metastatic fixation. These stage-resolved plasma signatures—ranging from NAMPT-linked metabolic priming to complement-driven EMT stabilization—offer a noninvasive framework for monitoring EMT-associated resistance and metastasis. To our knowledge, NAMPT has not previously been examined within EMT-focused plasma proteomics in CRC, highlighting the novelty of this approach while aligning with recent reports linking NAMPT to EMT, stemness, and drug resistance across cancers. The rising incidence of early-onset CRC (EOCRC), particularly in APAC populations, underscores the urgency of validating these plasma signatures in larger, longitudinal, and molecularly stratified cohorts. Together, this discovery-phase study provides regionally grounded yet globally relevant insights into EMT-linked progression and therapeutic resistance, warranting validation in expanded, longitudinal cohorts.
{"title":"Plasma proteomics reveals stage-specific EMT-linked signals: NAMPT in early and complement in advanced colorectal cancer","authors":"Raajesh Anand Natarajan , Siva Kaliyamoorthy , Vinoth Boopathi , Jawahar Ramasamy , Ravikumar Sambandam","doi":"10.1016/j.adcanc.2025.100165","DOIUrl":"10.1016/j.adcanc.2025.100165","url":null,"abstract":"<div><div>Epithelial–mesenchymal transition (EMT) plays a dual role in driving both metastatic progression and therapy resistance in colorectal cancer (CRC). To identify systemic EMT-related signals across disease stages, we performed stage-specific plasma proteomics in treatment-naïve CRC patients from an Asia–Pacific (APAC)-representative discovery cohort in India. EMT-associated proteins were curated using FANTOM5 and validated through MSigDB enrichment, with protein interaction networks constructed via STRING and GeneMANIA. We developed an EMT Progression and Resistance Index (EPRI) that integrates literature support, stage specificity, and clinical trial relevance to prioritize clinically meaningful effectors. EPRI identified NAMPT as a central hub enriched in Stage I plasma, consistent with metabolic priming via NAD<sup>+</sup> biosynthesis. A NAMPT-centered subnetwork revealed stage-dependent interactions spanning complement and metabolic pathways, implicating systemic redox remodeling and PI3K/Akt signaling in EMT-driven dissemination and 5-FU/FOLFOX resistance. In later stages (III–IV), plasma signatures consolidated into complement pathway activation (notably elevated C4A/B and CR1), reflecting immune remodeling and metastatic fixation. These stage-resolved plasma signatures—ranging from NAMPT-linked metabolic priming to complement-driven EMT stabilization—offer a noninvasive framework for monitoring EMT-associated resistance and metastasis. To our knowledge, NAMPT has not previously been examined within EMT-focused plasma proteomics in CRC, highlighting the novelty of this approach while aligning with recent reports linking NAMPT to EMT, stemness, and drug resistance across cancers. The rising incidence of early-onset CRC (EOCRC), particularly in APAC populations, underscores the urgency of validating these plasma signatures in larger, longitudinal, and molecularly stratified cohorts. Together, this discovery-phase study provides regionally grounded yet globally relevant insights into EMT-linked progression and therapeutic resistance, warranting validation in expanded, longitudinal cohorts.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"16 ","pages":"Article 100165"},"PeriodicalIF":3.0,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145925281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The metastasis process plays an important role in the outcome of all cancers, including breast cancer, a leading cause of cancer mortality in women. This study assessed the effects of gaillardin on the metastatic activity of two different breast cancer cell lines. The MTT assay was used to obtain the IC50 concentrations. Migration or metastatic capability of MCF7 and MDA-MB231 cell lines was assayed using the wound scratch assay. The real-time PCR was utilized to quantify the gene expression of epithelial-mesenchymal transition (EMT) markers CDH1, CDH2, VIM, and FN1, along with angiogenesis-related markers VEGFA and THBS1. Western blotting was conducted to estimate the protein expression of E-cadherin, N-cadherin, vimentin, fibronectin 1, VEGFA, and thrombospondin 1. Treatment of the MCF7 cell line with different concentrations of gaillardin revealed no significant effect on the metastatic capacity of these cancer cells compared with the controls. However, the migratory activity and aggressiveness of MDA-MB231 cells were significantly hindered compared to the control cells. The results of gene expression data revealed the upregulating effect of gaillardin on the expression of CDH1 and THBS1 genes. Conversely, this phytochemical significantly downregulated CDH2, VIM, FN1, and VEGFA transcripts. Western blotting results showed a similar effect of gaillardin on the expression levels of the above-mentioned markers. The present data highlight the anti-metastatic activity of gaillardin in breast cancer in a receptor-independent manner. These results also indicate gaillardin as a potential anti-metastatic natural compound against triple-negative breast cancer cells, via two mechanisms that act by suppressing EMT and angiogenesis.
{"title":"Effect of gaillardin on the metastatic capacity of breast cancer cells and its underlying mechanism","authors":"Sadegh Rajabi , Akram Shahhosseini , Mahboubeh Irani , Marc Maresca , Maryam Hamzeloo-Moghadam","doi":"10.1016/j.adcanc.2025.100164","DOIUrl":"10.1016/j.adcanc.2025.100164","url":null,"abstract":"<div><div>The metastasis process plays an important role in the outcome of all cancers, including breast cancer, a leading cause of cancer mortality in women. This study assessed the effects of gaillardin on the metastatic activity of two different breast cancer cell lines. The MTT assay was used to obtain the IC<sub>50</sub> concentrations. Migration or metastatic capability of MCF7 and MDA-MB231 cell lines was assayed using the wound scratch assay. The real-time PCR was utilized to quantify the gene expression of epithelial-mesenchymal transition (EMT) markers CDH1, CDH2, VIM, and FN1, along with angiogenesis-related markers VEGFA and THBS1. Western blotting was conducted to estimate the protein expression of E-cadherin, N-cadherin, vimentin, fibronectin 1, VEGFA, and thrombospondin 1. Treatment of the MCF7 cell line with different concentrations of gaillardin revealed no significant effect on the metastatic capacity of these cancer cells compared with the controls. However, the migratory activity and aggressiveness of MDA-MB231 cells were significantly hindered compared to the control cells. The results of gene expression data revealed the upregulating effect of gaillardin on the expression of CDH1 and THBS1 genes. Conversely, this phytochemical significantly downregulated CDH2, VIM, FN1, and VEGFA transcripts. Western blotting results showed a similar effect of gaillardin on the expression levels of the above-mentioned markers. The present data highlight the anti-metastatic activity of gaillardin in breast cancer in a receptor-independent manner. These results also indicate gaillardin as a potential anti-metastatic natural compound against triple-negative breast cancer cells, via two mechanisms that act by suppressing EMT and angiogenesis.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"15 ","pages":"Article 100164"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145617245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.adcanc.2025.100146
Wei Jin , Jue-jue Wang , Yan-fei Feng , Bing Chen , Zhao-hua Hu
{"title":"Corrigendum to “HDAC3-mediated deacetylation of p21 stabilizes protein levels and promotes 5-FU resistance in colorectal cancer cells” [ADCANC (2025) 100136]","authors":"Wei Jin , Jue-jue Wang , Yan-fei Feng , Bing Chen , Zhao-hua Hu","doi":"10.1016/j.adcanc.2025.100146","DOIUrl":"10.1016/j.adcanc.2025.100146","url":null,"abstract":"","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"15 ","pages":"Article 100146"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145683777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.adcanc.2025.100162
Yi Liu , JiaYing Ma , Jitian Zhang , Qi Sun
Lung cancer is the leading cause of cancer-related death globally and the most common cause of brain metastasis. Non-small cell lung cancer (NSCLC) accounts for approximately 80 % of all lung cancers. High metastasis and recurrence rates are important factors contributing to the poor prognosis of patients with NSCLC. The canonical WNT signaling pathway, as a highly conserved signal transduction pathway, not only directly affects the metastasis and recurrence of NSCLC, but also participates in it by regulating the stemness and epithelial-mesenchymal transition (EMT) process of lung cancer cells, or by interacting with other signaling pathways. In this review, we summarize the direct or indirect functions and mechanisms of roles of the WNT/β-catenin signaling pathway (including WNT ligands, β-catenin, glycogen synthase kinase 3Β, adenomatous polyposis coli, axis inhibition protein, dishevelled, frizzled serpentine receptor, Dickkopf-related protein, lymphoid enhancer-binding factor/T cell-specific factor, and S-phase kinase associated protein 1–cullin–F-box E3 ligase) in NSCLC metastasis and recurrence. Additionally, we explore the potential of inhibitors of this pathway in preventing NSCLC metastasis and recurrence.
{"title":"Roles of the WNT/β-catenin signaling pathway in the metastasis and recurrence of NSCLC","authors":"Yi Liu , JiaYing Ma , Jitian Zhang , Qi Sun","doi":"10.1016/j.adcanc.2025.100162","DOIUrl":"10.1016/j.adcanc.2025.100162","url":null,"abstract":"<div><div>Lung cancer is the leading cause of cancer-related death globally and the most common cause of brain metastasis. Non-small cell lung cancer (NSCLC) accounts for approximately 80 % of all lung cancers. High metastasis and recurrence rates are important factors contributing to the poor prognosis of patients with NSCLC. The canonical WNT signaling pathway, as a highly conserved signal transduction pathway, not only directly affects the metastasis and recurrence of NSCLC, but also participates in it by regulating the stemness and epithelial-mesenchymal transition (EMT) process of lung cancer cells, or by interacting with other signaling pathways. In this review, we summarize the direct or indirect functions and mechanisms of roles of the WNT/β-catenin signaling pathway (including WNT ligands, β-catenin, glycogen synthase kinase 3Β, adenomatous polyposis coli, axis inhibition protein, dishevelled, frizzled serpentine receptor, Dickkopf-related protein, lymphoid enhancer-binding factor/T cell-specific factor, and S-phase kinase associated protein 1–cullin–F-box E3 ligase) in NSCLC metastasis and recurrence. Additionally, we explore the potential of inhibitors of this pathway in preventing NSCLC metastasis and recurrence.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"15 ","pages":"Article 100162"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145617246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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