Pub Date : 2025-12-01Epub Date: 2025-10-22DOI: 10.1016/j.adcanc.2025.100158
Maryam Motallebinezhad , Ali Faravash , Mohammad Ghasemian , Zahra Tajik , Mohsen Ahmadi , Solat Eslami , Soudeh Ghafouri-Fard
As an imidazotetrazine derived from the alkylating substance dacarbazine, Temozolomide (TMZ) is commonly used as the routine chemotherapy for new cases of glioblastoma multiforme (GBM). It substantially improves the clinical outcome of patients. But, resistance to TMZ is regarded as a principal impediment in the postgenomic years of GBM management. Recent investigations showed the critical roles of lncRNAs, miRNAs and circRNAs and their interactions in GBM treatment. Remarkably, several miRNAs, such as miR-125b, miR-30b-3p, miR-24-3p, miR-590, miR-125b, and miR-7-5p regulate activity of glioma stem cells. Besides, a number of miRNAs, namely miR-370-3p, miR-198, miR-486-3p, miR-29c, miR-130a, miR-181 d, miR-198, miR-182-5p and miR-370-3p regulate expression of the DNA repair protein MGMT. Most of lncRNAs and circRNAs exert their role on TMZ resistance through sponging miRNAs. Notably, these transcripts have revolutionized the understanding about GBM pathogenesis and application of personalized medicine for this cancer. This review concentrates on the importance of these transcripts in resistance to TMZ in GBM patients.
{"title":"Temozolomide resistance in glioblastoma: a non-coding RNA viewpoint","authors":"Maryam Motallebinezhad , Ali Faravash , Mohammad Ghasemian , Zahra Tajik , Mohsen Ahmadi , Solat Eslami , Soudeh Ghafouri-Fard","doi":"10.1016/j.adcanc.2025.100158","DOIUrl":"10.1016/j.adcanc.2025.100158","url":null,"abstract":"<div><div>As an imidazotetrazine derived from the alkylating substance dacarbazine, Temozolomide (TMZ) is commonly used as the routine chemotherapy for new cases of glioblastoma multiforme (GBM). It substantially improves the clinical outcome of patients. But, resistance to TMZ is regarded as a principal impediment in the postgenomic years of GBM management. Recent investigations showed the critical roles of lncRNAs, miRNAs and circRNAs and their interactions in GBM treatment. Remarkably, several miRNAs, such as miR-125b, miR-30b-3p, miR-24-3p, miR-590, miR-125b, and miR-7-5p regulate activity of glioma stem cells. Besides, a number of miRNAs, namely miR-370-3p, miR-198, miR-486-3p, miR-29c, miR-130a, miR-181 d, miR-198, miR-182-5p and miR-370-3p regulate expression of the DNA repair protein MGMT. Most of lncRNAs and circRNAs exert their role on TMZ resistance through sponging miRNAs. Notably, these transcripts have revolutionized the understanding about GBM pathogenesis and application of personalized medicine for this cancer. This review concentrates on the importance of these transcripts in resistance to TMZ in GBM patients.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"15 ","pages":"Article 100158"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145361068","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 : 2025-12-01Epub Date: 2025-09-26DOI: 10.1016/j.adcanc.2025.100154
Yunfan Wang , Ke Min , Jun Shi , Jun Jin , Qiang Yao , Jianping Zhou , Weimin Wang
Background
Gastric cancer (GC) is a common digestive malignancy with high mortality, primarily due to liver metastasis. The underlying molecular mechanisms driving this process remain poorly understood. This study aimed to identify novel prognostic biomarkers for GC liver metastasis.
Methods
We analyzed mRNA expression data from non-metastatic, liver-metastatic, and other-metastatic GC patient samples from The Cancer Genome Atlas (TCGA) database. Weighted gene co-expression network analysis (WGCNA) was employed to identify key gene modules and hub genes associated with liver metastasis. Potential biomarkers were screened based on differential expression, prognostic value determined by Kaplan-Meier survival analysis, and risk assessment via a univariate Cox regression model. The findings were then validated in an independent cohort of 380 GC patients.
Results
The WGCNA identified a gene module (MEgrey) significantly correlated with GC liver metastasis. Within this module, TMEM119 and NRXN2 were identified as key hub genes whose expression was significantly higher in the liver metastasis group compared to the non-metastatic and other-metastatic groups. High expression of either TMEM119 or NRXN2 was associated with shorter overall survival (OS) and indicated an increased risk of mortality (HR > 1). These findings were confirmed in our validation cohort.
Conclusion
TMEM119 and NRXN2 are promising prognostic biomarkers for predicting liver metastasis in GC patients and may serve as potential therapeutic targets.
{"title":"TMEM119 and NRXN2 as prognostic biomarkers for liver metastasis in gastric cancer","authors":"Yunfan Wang , Ke Min , Jun Shi , Jun Jin , Qiang Yao , Jianping Zhou , Weimin Wang","doi":"10.1016/j.adcanc.2025.100154","DOIUrl":"10.1016/j.adcanc.2025.100154","url":null,"abstract":"<div><h3>Background</h3><div>Gastric cancer (GC) is a common digestive malignancy with high mortality, primarily due to liver metastasis. The underlying molecular mechanisms driving this process remain poorly understood. This study aimed to identify novel prognostic biomarkers for GC liver metastasis.</div></div><div><h3>Methods</h3><div>We analyzed mRNA expression data from non-metastatic, liver-metastatic, and other-metastatic GC patient samples from The Cancer Genome Atlas (TCGA) database. Weighted gene co-expression network analysis (WGCNA) was employed to identify key gene modules and hub genes associated with liver metastasis. Potential biomarkers were screened based on differential expression, prognostic value determined by Kaplan-Meier survival analysis, and risk assessment via a univariate Cox regression model. The findings were then validated in an independent cohort of 380 GC patients.</div></div><div><h3>Results</h3><div>The WGCNA identified a gene module (MEgrey) significantly correlated with GC liver metastasis. Within this module, TMEM119 and NRXN2 were identified as key hub genes whose expression was significantly higher in the liver metastasis group compared to the non-metastatic and other-metastatic groups. High expression of either TMEM119 or NRXN2 was associated with shorter overall survival (OS) and indicated an increased risk of mortality (HR > 1). These findings were confirmed in our validation cohort.</div></div><div><h3>Conclusion</h3><div>TMEM119 and NRXN2 are promising prognostic biomarkers for predicting liver metastasis in GC patients and may serve as potential therapeutic targets.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"15 ","pages":"Article 100154"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145219419","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 : 2025-12-01Epub Date: 2025-08-02DOI: 10.1016/j.adcanc.2025.100147
Ligang Ma , Ruixin Li , Junjie Su , Qiong Cao , Haojie Wang , Zhihao Wei , Chengliang Wang , Chengdong Zhang , Guanyu Li , Wang Qin , Zheng Zhang , Chu Wang , Yingao Zhu , Jingjing Zhao , Shiyong Xin , Jun Ma
Background
With increasing evidence indicating that immune cells significantly contribute to tumor progression, elucidating their role in tumor prognosis and therapy has become imperative. This study aims to thoroughly characterize tumor-infiltrating immune cells in bladder cancer (BLCA) and identify key immune cells and gene models associated with prognosis and therapeutic outcomes in BLCA.
Methods
Initially, we assessed the relationship between the abundance of infiltrating immune cells and prognosis, CD8+T cell was selected to establish the risk model, which was constructed based on five key genes. Then ROC curve was drawn to demonstrate the risk model had high prognosis predictive value in BLCA.
Results
Our correlation analysis revealed that riskscore was negatively associated with several steps of the tumor immune cycle. Additionally, the risk score exhibited a negative correlation with the expression levels of CD8,CD274,IFNG, Merck18, and several common immune checkpoints. Furthermore, the tumor exclusion score and Tumor Immune Dysfunction and Exclusion (TIDE) score were significantly higher in the high-score group compared to the low-score group. Notably, the risk score demonstrated a negative correlation with the enrichment score of immunotherapy-related pathways, indicating that the therapeutic benefit was greater in the low-score group than in the high-score group. Then, a total of 171 chemotherapy and targeted drugs were identified. Subsequently, immunohistochemistry, EDU and Western blot were used to verify our result.
Conclusions
Our results confirmed that the tumor infiltration CD8+ T cells in tumors plays a critical role in the prognosis and treatment of bladder cancer (BLCA). This insight may offer new directions and inspiration for prognostic prediction and therapeutic strategies for bladder cancer in the future.
{"title":"Identification of a risk model for prognostic and therapeutic prediction in bladder urothelial carcinoma based on infiltrating CD8+ T cells","authors":"Ligang Ma , Ruixin Li , Junjie Su , Qiong Cao , Haojie Wang , Zhihao Wei , Chengliang Wang , Chengdong Zhang , Guanyu Li , Wang Qin , Zheng Zhang , Chu Wang , Yingao Zhu , Jingjing Zhao , Shiyong Xin , Jun Ma","doi":"10.1016/j.adcanc.2025.100147","DOIUrl":"10.1016/j.adcanc.2025.100147","url":null,"abstract":"<div><h3>Background</h3><div>With increasing evidence indicating that immune cells significantly contribute to tumor progression, elucidating their role in tumor prognosis and therapy has become imperative. This study aims to thoroughly characterize tumor-infiltrating immune cells in bladder cancer (BLCA) and identify key immune cells and gene models associated with prognosis and therapeutic outcomes in BLCA.</div></div><div><h3>Methods</h3><div>Initially, we assessed the relationship between the abundance of infiltrating immune cells and prognosis, CD8<sup>+</sup>T cell was selected to establish the risk model, which was constructed based on five key genes. Then ROC curve was drawn to demonstrate the risk model had high prognosis predictive value in BLCA.</div></div><div><h3>Results</h3><div>Our correlation analysis revealed that riskscore was negatively associated with several steps of the tumor immune cycle. Additionally, the risk score exhibited a negative correlation with the expression levels of CD8,CD274,IFNG, Merck18, and several common immune checkpoints. Furthermore, the tumor exclusion score and Tumor Immune Dysfunction and Exclusion (TIDE) score were significantly higher in the high-score group compared to the low-score group. Notably, the risk score demonstrated a negative correlation with the enrichment score of immunotherapy-related pathways, indicating that the therapeutic benefit was greater in the low-score group than in the high-score group. Then, a total of 171 chemotherapy and targeted drugs were identified. Subsequently, immunohistochemistry, EDU and Western blot were used to verify our result.</div></div><div><h3>Conclusions</h3><div>Our results confirmed that the tumor infiltration CD8<sup>+</sup> T cells in tumors plays a critical role in the prognosis and treatment of bladder cancer (BLCA). This insight may offer new directions and inspiration for prognostic prediction and therapeutic strategies for bladder cancer in the future.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"15 ","pages":"Article 100147"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144758097","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 : 2025-12-01Epub Date: 2025-07-02DOI: 10.1016/j.adcanc.2025.100142
Zahra Tajik, Soudeh Ghafouri-Fard
As a chemotherapeutic agent, gemcitabine makes the backbone of several chemotherapeutic regimens, particularly those used for advanced cancers. However, drug resistance confines the long-term therapeutic impact of gemcitabine in cancer treatment and makes the patients' prognosis poor. Several mechanisms such as alteration of membrane transporters, abnormal regulation of activating and inactivating enzymes, and alterations in signaling pathway have been proposed for induction of resistance to gemcitabine. However, none of them could individually explain the varied spectrum of patients' responses to this agent. Recent recognition of the role of circular RNAs (circRNAs) in the pathoetiology of cancer has opened a new venue for identification of molecular events leading to chemoresistance. The current review provides insights into the role of specific circRNAs in determination of response to gemcitabine.
{"title":"CircRNAs modulate response of cancer cells to gemcitabine","authors":"Zahra Tajik, Soudeh Ghafouri-Fard","doi":"10.1016/j.adcanc.2025.100142","DOIUrl":"10.1016/j.adcanc.2025.100142","url":null,"abstract":"<div><div>As a chemotherapeutic agent, gemcitabine makes the backbone of several chemotherapeutic regimens, particularly those used for advanced cancers. However, drug resistance confines the long-term therapeutic impact of gemcitabine in cancer treatment and makes the patients' prognosis poor. Several mechanisms such as alteration of membrane transporters, abnormal regulation of activating and inactivating enzymes, and alterations in signaling pathway have been proposed for induction of resistance to gemcitabine. However, none of them could individually explain the varied spectrum of patients' responses to this agent. Recent recognition of the role of circular RNAs (circRNAs) in the pathoetiology of cancer has opened a new venue for identification of molecular events leading to chemoresistance. The current review provides insights into the role of specific circRNAs in determination of response to gemcitabine.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"15 ","pages":"Article 100142"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144534955","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 : 2025-12-01Epub Date: 2025-11-13DOI: 10.1016/j.adcanc.2025.100161
Zahra Gharedaghi , Parichehr Mehrafshar , Soha Mohammadi , Masoumeh Tavakoli-Yaraki , Pegah Golpour , Mitra Nourbakhsh , Nima Taghizadeh
Introduction
Two pathways in the synthesis of NAD, catalyzed by the key enzymes nicotinamide phosphoribosyltransferase (NAMPT) and nicotinate phosphoribosyltransferase (NAPRT), support constant survival, growth, and propagation of cancer cells. This study investigated the effect of the NAMPT inhibitor FK866 combined with 2-Hydroxynicotinic Acid (2-HNA), an inhibitor of nicotinate phosphoribosyltransferase (NAPRT), on breast cancer cell survival, apoptosis, and metastasis.
Methods
MCF-7 and MDA-MB-231 breast cancer cells were cultured and treated with FK866, 2-HNA, or their combinations. Cell viability and apoptosis were evaluated using the MTT assay and Annexin V staining. The effect of inhibitors on p21, BAX, and p53 gene expression was assessed after RNA extraction and cDNA synthesis by real-time PCR using gene-specific primers. Cell migration and invasion were investigated using a scratch assay and matrigel penetration, respectively.
Results
The combination of inhibitors showed synergistic and additive effects in reducing cell viability in MCF-7 and MDA-MB-231 cells, respectively. Both inhibitors induced apoptosis and decreased invasion and migration in breast cancer cells; however, co-treatment was more effective than monotherapy. They significantly enhanced pro-apoptotic gene expression of p53, p21, and BAX, with co-treatment showing greater efficacy in both cell lines.
Conclusion
Simultaneous inhibition of NAMPT and NAPRT reduced cell viability, induced apoptosis, and inhibited metastasis of breast cancer cells. Therefore, targeting NAPRT in addition to NAMPT may offer a more effective therapeutic strategy for breast cancer.
{"title":"Enhancing the anticancer effect of NAMPT inhibition by targeting NAPRT in breast cancer cells","authors":"Zahra Gharedaghi , Parichehr Mehrafshar , Soha Mohammadi , Masoumeh Tavakoli-Yaraki , Pegah Golpour , Mitra Nourbakhsh , Nima Taghizadeh","doi":"10.1016/j.adcanc.2025.100161","DOIUrl":"10.1016/j.adcanc.2025.100161","url":null,"abstract":"<div><h3>Introduction</h3><div>Two pathways in the synthesis of NAD, catalyzed by the key enzymes nicotinamide phosphoribosyltransferase (NAMPT) and nicotinate phosphoribosyltransferase (NAPRT), support constant survival, growth, and propagation of cancer cells. This study investigated the effect of the NAMPT inhibitor FK866 combined with 2-Hydroxynicotinic Acid (2-HNA), an inhibitor of nicotinate phosphoribosyltransferase (NAPRT), on breast cancer cell survival, apoptosis, and metastasis.</div></div><div><h3>Methods</h3><div>MCF-7 and MDA-MB-231 breast cancer cells were cultured and treated with FK866, 2-HNA, or their combinations. Cell viability and apoptosis were evaluated using the MTT assay and Annexin V staining. The effect of inhibitors on p21, BAX, and p53 gene expression was assessed after RNA extraction and cDNA synthesis by real-time PCR using gene-specific primers. Cell migration and invasion were investigated using a scratch assay and matrigel penetration, respectively.</div></div><div><h3>Results</h3><div>The combination of inhibitors showed synergistic and additive effects in reducing cell viability in MCF-7 and MDA-MB-231 cells, respectively. Both inhibitors induced apoptosis and decreased invasion and migration in breast cancer cells; however, co-treatment was more effective than monotherapy. They significantly enhanced pro-apoptotic gene expression of p53, p21, and BAX, with co-treatment showing greater efficacy in both cell lines.</div></div><div><h3>Conclusion</h3><div>Simultaneous inhibition of NAMPT and NAPRT reduced cell viability, induced apoptosis, and inhibited metastasis of breast cancer cells. Therefore, targeting NAPRT in addition to NAMPT may offer a more effective therapeutic strategy for breast cancer.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"15 ","pages":"Article 100161"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145571317","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 : 2025-12-01Epub Date: 2025-07-09DOI: 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}
Long non-coding RNAs (lncRNAs) have important roles in gene regulation and disease pathogenesis. Among them, PTPRG-AS1 (Protein Tyrosine Phosphatase Receptor Type G Antisense RNA 1) has emerged as a potential player in several cancers, particularly breast cancer. This lncRNA has also been found to be over-expressed in nasopharyngeal carcinoma and lung cancer, among other cancers. Moreover, up-regulation of this lncRNA is associated with metastatic potential of gastric cancer, epithelial ovarian cancer, osteosarcoma, hepatocellular carcinoma and triple negative breast cancer. Several microRNAs have been reported as potential interacting molecules with PTPRG-AS1. This article explores the role of PTPRG-AS1 through a literature-based review and bioinformatics analysis, highlighting its molecular mechanisms, expression patterns, and clinical implications. The data summarized in this review may help design of novel anti-cancer therapies, particularly focusing on combating cancer hallmarks, such as stemness and invasion. However, further experimental validation is needed before implementation of these results in the clinical settings.
{"title":"The multifaceted functions of lncRNA PTPRG-AS1 in human cancers: An in-depth investigation through extensive bioinformatic analyses and literature review","authors":"Mohsen Ahmadi , Zahra Tajik , Kiana Salmani , Fatemeh Ghadyani , Soudeh Ghafouri-Fard","doi":"10.1016/j.adcanc.2025.100159","DOIUrl":"10.1016/j.adcanc.2025.100159","url":null,"abstract":"<div><div>Long non-coding RNAs (lncRNAs) have important roles in gene regulation and disease pathogenesis. Among them, PTPRG-AS1 (Protein Tyrosine Phosphatase Receptor Type G Antisense RNA 1) has emerged as a potential player in several cancers, particularly breast cancer. This lncRNA has also been found to be over-expressed in nasopharyngeal carcinoma and lung cancer, among other cancers. Moreover, up-regulation of this lncRNA is associated with metastatic potential of gastric cancer, epithelial ovarian cancer, osteosarcoma, hepatocellular carcinoma and triple negative breast cancer. Several microRNAs have been reported as potential interacting molecules with PTPRG-AS1. This article explores the role of PTPRG-AS1 through a literature-based review and bioinformatics analysis, highlighting its molecular mechanisms, expression patterns, and clinical implications. The data summarized in this review may help design of novel anti-cancer therapies, particularly focusing on combating cancer hallmarks, such as stemness and invasion. However, further experimental validation is needed before implementation of these results in the clinical settings.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"15 ","pages":"Article 100159"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145361056","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 : 2025-12-01Epub Date: 2025-07-02DOI: 10.1016/j.adcanc.2025.100143
XianYi Zhou , JiuLin Li , XiuYong Liao , ChengYu Ding , SaiJiao Na , JiangRong Du , QingHui Meng , Peng Zheng , Fan Sun
DSF is a well-known alcohol withdrawal agent that has shown considerable anticancer effects in preclinical studies. In the present study, we aimed to elucidate the mechanism by which DSF and CTSB modulate of the migration and invasion of GCs. Our results illustrate that DSF plays a pivotal role in suppressing tumor migration, invasion, and EMT in GC by modulating CTSB expression. Furthermore, DSF was found to aggravate the reduction in β-catenin expression via GSK-3β, consequently inhibiting CTSB expression, which has a pronounced effect on invading gastric cancer cells as a metastasis-promoting gene. Notably, β-catenin was found to increase CTSB transcriptional activity by binding to the promoter of CTSB, leading to an increase in CTSB protein levels. Collectively, our findings elucidate the molecular mechanism by which DSF suppresses EMT, migration, and invasion in GC through the GSK-3β/β-catenin/CTSB pathway, underscoring the potential of CTSB as a therapeutic target for GC.
{"title":"Disulfiram inhibits migration, invasion and epithelial-mesenchymal transition of gastric cancer cells via β-catenin/CTSB pathway","authors":"XianYi Zhou , JiuLin Li , XiuYong Liao , ChengYu Ding , SaiJiao Na , JiangRong Du , QingHui Meng , Peng Zheng , Fan Sun","doi":"10.1016/j.adcanc.2025.100143","DOIUrl":"10.1016/j.adcanc.2025.100143","url":null,"abstract":"<div><div>DSF is a well-known alcohol withdrawal agent that has shown considerable anticancer effects in preclinical studies. In the present study, we aimed to elucidate the mechanism by which DSF and CTSB modulate of the migration and invasion of GCs. Our results illustrate that DSF plays a pivotal role in suppressing tumor migration, invasion, and EMT in GC by modulating CTSB expression. Furthermore, DSF was found to aggravate the reduction in β-catenin expression via GSK-3β, consequently inhibiting CTSB expression, which has a pronounced effect on invading gastric cancer cells as a metastasis-promoting gene. Notably, β-catenin was found to increase CTSB transcriptional activity by binding to the promoter of CTSB, leading to an increase in CTSB protein levels. Collectively, our findings elucidate the molecular mechanism by which DSF suppresses EMT, migration, and invasion in GC through the GSK-3β/β-catenin/CTSB pathway, underscoring the potential of CTSB as a therapeutic target for GC.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"15 ","pages":"Article 100143"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144534954","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}
Vasculogenic Mimicry (VM) is a distinct mode of tumor vascularization, separate from angiogenesis, whereby highly invasive cancer cells form functional vascular-like structures to facilitate the transport of blood and tumor cells. Unlike angiogenesis, which is mediated by endothelial cells, VM is exclusively driven by cancer cells and is recognized as a pivotal mechanism in breast cancer progression. This review is designed to elucidate the cellular and molecular mechanisms underpinning VM in breast cancer metastasis, with emphasis placed on the contributions of the tumor microenvironment, epithelial-mesenchymal transition (EMT), and cancer stem cells (CSCs). The involvement of key signaling pathways, such as EphA2/PIK3R1/CTNNB1, is also examined. Furthermore, the role of VM in promoting tumor growth, invasion, and distant metastasis is analyzed, alongside its contribution to resistance against established anti-angiogenic therapies. The therapeutic potential of targeting VM is explored, encompassing the development of specific inhibitors and combination therapy strategies. Additionally, the utility of VM as a prognostic and predictive marker in breast cancer is evaluated, and future research directions, along with challenges in clinical translation, are outlined.
{"title":"The mechanisms of action and targeting potential of vasculogenic mimicry in breast cancer metastasis","authors":"Cangtai Guan, Liangyu Hao, Biyou Gong, Lixiang Zheng","doi":"10.1016/j.adcanc.2025.100153","DOIUrl":"10.1016/j.adcanc.2025.100153","url":null,"abstract":"<div><div>Vasculogenic Mimicry (VM) is a distinct mode of tumor vascularization, separate from angiogenesis, whereby highly invasive cancer cells form functional vascular-like structures to facilitate the transport of blood and tumor cells. Unlike angiogenesis, which is mediated by endothelial cells, VM is exclusively driven by cancer cells and is recognized as a pivotal mechanism in breast cancer progression. This review is designed to elucidate the cellular and molecular mechanisms underpinning VM in breast cancer metastasis, with emphasis placed on the contributions of the tumor microenvironment, epithelial-mesenchymal transition (EMT), and cancer stem cells (CSCs). The involvement of key signaling pathways, such as EphA2/PIK3R1/CTNNB1, is also examined. Furthermore, the role of VM in promoting tumor growth, invasion, and distant metastasis is analyzed, alongside its contribution to resistance against established anti-angiogenic therapies. The therapeutic potential of targeting VM is explored, encompassing the development of specific inhibitors and combination therapy strategies. Additionally, the utility of VM as a prognostic and predictive marker in breast cancer is evaluated, and future research directions, along with challenges in clinical translation, are outlined.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"15 ","pages":"Article 100153"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157170","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 : 2025-12-01Epub Date: 2025-08-05DOI: 10.1016/j.adcanc.2025.100148
April Kirkendoll
The emergence of cancer is a multistep process, with passage through a so-called precancerous stage as part of the development. Biopsies of suspicious lesions often reveal cells that are altered or abnormal, and those anomalous cells, while often still benign, indicate local conditions conducive to carcinogenesis. Most of the altered cells never develop into cancers, and it is unknown what may trigger malignancy. This report reexamines existing data to provide insights into the conditions necessary to prime a relatively benign and latent cell with malignant potential to respond to a stimulus and transform into cancer. I propose that normal, well-established reactions to cellular insults over time induce conditions within the affected cell which predispose it to malignant transformation. Then, cumulative, age-related changes in the stromal milieu, from a burgeoning population of senescent cells, inadvertently facilitates the progression of mutant cells, contributing to the increase in late life cancers, via incremental seclusion from normal somatic tissues. Within an increasingly exclusive compartment, cells begin a cycle of crosstalk upon each other, incrementally modifying the isolated population of cells with multiple dynamic morphogen gradients that converge, amplify, and erase epigenetic memory within the innermost cells, reprogramming them to a stem cell-like state, and priming them to transform into a novel tissue.
{"title":"Latency, microenvironment, and the priming of a precancerous senescent cell for malignant transformation","authors":"April Kirkendoll","doi":"10.1016/j.adcanc.2025.100148","DOIUrl":"10.1016/j.adcanc.2025.100148","url":null,"abstract":"<div><div>The emergence of cancer is a multistep process, with passage through a so-called precancerous stage as part of the development. Biopsies of suspicious lesions often reveal cells that are altered or abnormal, and those anomalous cells, while often still benign, indicate local conditions conducive to carcinogenesis. Most of the altered cells never develop into cancers, and it is unknown what may trigger malignancy. This report reexamines existing data to provide insights into the conditions necessary to prime a relatively benign and latent cell with malignant potential to respond to a stimulus and transform into cancer. I propose that normal, well-established reactions to cellular insults over time induce conditions within the affected cell which predispose it to malignant transformation. Then, cumulative, age-related changes in the stromal milieu, from a burgeoning population of senescent cells, inadvertently facilitates the progression of mutant cells, contributing to the increase in late life cancers, via incremental seclusion from normal somatic tissues. Within an increasingly exclusive compartment, cells begin a cycle of crosstalk upon each other, incrementally modifying the isolated population of cells with multiple dynamic morphogen gradients that converge, amplify, and erase epigenetic memory within the innermost cells, reprogramming them to a stem cell-like state, and priming them to transform into a novel tissue.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"15 ","pages":"Article 100148"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144779774","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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