Advances in cancer biology - metastasis最新文献

{"title":"Anticancer efficacy of 2-Hydroxy-4-methoxybenzoic acid through dual regulation of lactate transport via inhibition of MCT-1 and MCT-4","authors":"Sneha Yadav ,&nbsp;Jyoti Singh ,&nbsp;Rohit Kumar ,&nbsp;Archana Bharti Sonkar ,&nbsp;Anurag Kumar ,&nbsp;Dharmendra Kumar ,&nbsp;Neeraj Kumar Shrivastava ,&nbsp;Mohd Nazam Ansari ,&nbsp;Abdulaziz S. Saeedan ,&nbsp;Sara A. Aldossary ,&nbsp;Gaurav Kaithwas","doi":"10.1016/j.adcanc.2025.100163","DOIUrl":"10.1016/j.adcanc.2025.100163","url":null,"abstract":"<div><div>Monocarboxylate transporters (MCTs) play critical role in the progression of mammary gland carcinoma. The unregulated cell growth increased glycolytic phenotype via glycolysis pathway which leads to concomitant synthesis of lactate. Lactate facilitates acidification of tumour microenvironment (TME), metastasis, and immune evasion. Thus, MCTs inhibition has emerged as a novel approach to treat mammary gland carcinoma. Herein, the current study aim to identify and validate small molecule as dual MCT-1 and MCT-4 inhibitor for mammary gland chemoprevention. We performed structure based virtual screening of natural based library (<span><span>HY-L057L</span><svg><path></path></svg></span>) and outcomes underscore 2-Hydroxy-4-methoxybenzoic acid (HMBA) as potential compound. HMBA demonstrated higher molecular docking score, favourable ADMET profiling and drug-likeness.Moreover, HMBA was examined for its cytotoxicity and apoptotic activity via <em>in-vitro</em> studies on MCF-7 cells. The results showed that HMBA possessed a substantial IC50 value of 4.8 μM and having apoptotic potential. Additionally, we tested its anticancer effects against a 7,12- dimethylbenz[a]anthracene) (DMBA)-induced tumour model <em>in-vivo</em>. Our findings demonstrated that the HMBA effectively corrected the altered histology and morphology. The altered levels of lactate and antioxidant were also restored by HMBA. In addition, HMBA regulate the mitochondrial apoptotic pathway and inhibit the hypoxia and angiogenesis and the lactate exchange transporters proteins, according to the results of the western blotting. The overall findings obtained from <em>in-silico</em>, <em>in-vitro</em>, and <em>in-vivo</em> studies present strong evidence for the pre-clinical effectiveness of HMBA in treating mammary gland carcinoma through dual inhibition of MCT-1 and MCT-4 and may pave the way for more Investigational New Drug (IND) compliance testing.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"16 ","pages":"Article 100163"},"PeriodicalIF":3.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145685380","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}

{"title":"Alcohol-induced extracellular vesicle signatures: Exploring liquid biopsy biomarkers for early cancer detection and prognosis","authors":"Neeraj Choudhary ,&nbsp;Dinesh Kumar ,&nbsp;Thakur Prava Jyoti ,&nbsp;Md Moidul Islam ,&nbsp;Suresh Babu Kondaveeti ,&nbsp;Md Faiyazuddin ,&nbsp;Thomas J. Webster","doi":"10.1016/j.adcanc.2026.100176","DOIUrl":"10.1016/j.adcanc.2026.100176","url":null,"abstract":"<div><div>Alcohol intake is a significant causative factor of cancer, affecting liver, colorectal, oral/esophageal, and breast cancers. The toxicity of alcohol is due to the breakdown of acetaldehyde that damages DNA, interferes with metabolism, and generates oxidative stress. Such alterations undermine the immune system, disrupt the surrounding tissue environment, and create the conditions for cancer development. Extracellular vesicles (EVs), small particles released by cells, are a relatively recent development as important mediators of cancer. EVs are also released in greater amounts and are augmented with microRNAs, mitochondrial DNA, proteins, lipids and metabolites when under alcohol exposure. Signals contained in these vesicles propagate injury, cause inflammation, induce fibrosis, favor the development of new blood vessels, and facilitate the survival and proliferation of cancer cells. Notably, EVs have been observed in blood, saliva, and other body fluids, which means that they can be used as non-invasive tools from a non-liquid biopsy. They are not only indicators of tissue injury, but also actively mediate cancer biology. The present manuscript is a thorough review of alcohol-associated EV patterns in various cancers and highlights how they can be used as a biomarker in the early diagnosis, prognosis, and treatment of cancer. EV-based markers have proven to be more sensitive and specific as compared to traditional blood tests, including AFP and CEA, especially in the detection of cancer in the early stage or predicting resistance to treatment. The present literature provides a summary of alcohol-induced EVs profiles in various cancers, making them dynamic effectors of carcinogenesis as well as biomarkers with clinical relevance, but also multi-omic EV profiles are the most appropriate compared to diagnostic/prognostic conventional markers of cancer. The priorities for the clinical translation of EVs to the clinical setting are in the need to develop unit protocols that can be used to isolate and analyze EVs and formulate alcohol-specific patient cohorts that can reflect genetic and lifestyle differences that affect biomarker performance. To pass regulatory validation and use the multi-omic EVs in practice, it will be necessary to validate them in large, well-characterized populations. The combination of these strategies makes alcohol-induced EV signatures some of the most effective precision oncology and personalized cancer treatment tools to date.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"16 ","pages":"Article 100176"},"PeriodicalIF":3.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147384862","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}

{"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 ,&nbsp;Raeann M. Koren Shimak ,&nbsp;Sumedha Gunewardena ,&nbsp;Dani Alexander ,&nbsp;Karen L. Wendt ,&nbsp;Stacey L. Hembruff ,&nbsp;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":"2026-07-01","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}

{"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":"2026-07-01","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}

{"title":"Histone demethylase KDM6B inhibitor GSK-J4 sensitizes glioma cells to tyrosine kinase inhibitor anlotinib in vitro by reducing PDGFRA expression","authors":"Biaogang Han ,&nbsp;Juan Li ,&nbsp;Li Li ,&nbsp;Yongqing Shen ,&nbsp;Xiaoqiang Guo ,&nbsp;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":"2026-07-01","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}

{"title":"Decoding YAP's role in oral cancer metastasis: A systematic synthesis of experimental and clinical evidence","authors":"Erfan Latifian ,&nbsp;Hesam Mobaraki ,&nbsp;Mohammad Hossein Aliasgharzadeh ,&nbsp;Mohammad Sina Saeidi ,&nbsp;Mahdi Habibzadeh ,&nbsp;Mohammad Arshia Naseri ,&nbsp;Arshia Alhosseini ,&nbsp;Komeil Aghazadeh-Habashi ,&nbsp;Farnoud Dadkhah Tehrani ,&nbsp;Sepehr Ramezanipour ,&nbsp;Kosar Mohammadnejad ,&nbsp;Seyed Mahdi Arfazadeh ,&nbsp;Sepehr Ghanavati ,&nbsp;Mohammad Hossein Darashti ,&nbsp;Mohammad Amiri ,&nbsp;Mahsa Asadi Anar ,&nbsp;Farbod Khosravi","doi":"10.1016/j.adcanc.2026.100177","DOIUrl":"10.1016/j.adcanc.2026.100177","url":null,"abstract":"<div><h3>Background</h3><div>Yes-associated protein (YAP), the key effector of Hippo signaling, is implicated in oncogenesis and metastasis in oral squamous cell carcinoma (OSCC). Prior reports vary in assay, model, and outcome definitions, limiting clear clinical translation.</div></div><div><h3>Methods</h3><div>Following PRISMA 2020, we searched PubMed, Scopus, and Web of Science to February 2025 for original studies evaluating YAP in OSCC across clinical, in vitro, and in vivo models. Data items included assay type, subcellular localization, phenotypic outcomes, and comparators. Risk of bias was assessed using the ROBINS-I tool. Given the heterogeneity, we used Synthesis Without Meta-analysis with direction-of-effect tabulation across prespecified domains: epithelial-to-mesenchymal transition, migration or invasion, in vivo tumor growth, and clinical survival. We also prespecified effect-modifier reporting for HPV or p16 status, immune contexture, and treatment modality.</div></div><div><h3>Results</h3><div>Thirteen studies met criteria. Healthy oral mucosa comparators were absent; one study included dysplasia. Demographic variables were inconsistently reported and were not pooled. Most studies used immunohistochemistry or western blot, with frequent emphasis on nuclear YAP localization as a proxy for activity. ROBINS-I judgments were mainly moderate risk, with one serious judgment; excluding the latter did not change conclusions. Direction-of-effect synthesis showed high consistency: pro-oncogenic direction in 12 of 13 studies overall; by domain, unfavorable direction in all studies assessing epithelial-to-mesenchymal transition, migration or invasion, and in vivo tumor growth, and in three of four studies assessing survival, with one favorable survival signal in a ferroptosis-linked context. Early clinical translation of TEAD inhibitors (IK-930 and VT3989) is underway in tumor-agnostic trials, although OSCC-specific efficacy data are not yet available.</div></div><div><h3>Conclusions</h3><div>Evidence across models supports YAP as a strong candidate driver of aggressive OSCC biology and a promising therapeutic target whose independent prognostic and predictive roles require prospective validation. Standardised evaluation is needed, including antibody metadata and validation, quantitative nuclear scoring and nuclear-to-cytoplasmic ratios, phospho-YAP, and a small TEAD target-gene panel. Future OSCC studies should stratify by HPV or p16 status, immune contexture, and treatment to clarify prognostic independence and to guide biomarker-selected trials of TEAD inhibition.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"16 ","pages":"Article 100177"},"PeriodicalIF":3.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147384863","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}

{"title":"Effect of gaillardin on the metastatic capacity of breast cancer cells and its underlying mechanism","authors":"Sadegh Rajabi ,&nbsp;Akram Shahhosseini ,&nbsp;Mahboubeh Irani ,&nbsp;Marc Maresca ,&nbsp;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 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.</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}

{"title":"The role of pseudogenes in breast cancer: from non-coding relics to functional regulators","authors":"Parisa Esmaeili Motalgh,&nbsp;Mohsen Ahmadi,&nbsp;Soudeh Ghafouri-Fard","doi":"10.1016/j.adcanc.2025.100152","DOIUrl":"10.1016/j.adcanc.2025.100152","url":null,"abstract":"<div><div>Pseudogenes were historically considered non-functional genomic relics. However, they are now acknowledged as possible regulators in various biological processes, including cancer. In breast cancer, emerging evidence implies the critical roles of pseudogenes in tumorigenesis, progression, and metastasis. These roles are mediated through mechanisms such as competitive endogenous RNA (ceRNA) activity, modulation of gene expression, and interaction with signaling pathways. Some pseudogenes, such as <em>DUXAP8, CYP4Z2P</em>, <em>RPSAP52</em>, <em>POU5F1P1</em>, <em>POU5F1P3</em>, <em>POU5F1P4</em> and <em>OCT4-PG1</em> exhibit dysregulated expression in breast cancer tissues, influencing oncogenic or tumor-suppressive pathways. Dysregulation of several pseudogenes has been associated with reduced survival of patients. Additionally, their ability to mimic parental genes or sequester microRNAs highlights their functional significance in disease pathogenesis. Despite challenges in differentiating pseudogenes from their parental genes, advancements in genomic technologies have enabled deeper exploration of their biological roles. This review summarizes current knowledge on pseudogene involvement in breast cancer, emphasizing their potential as biomarkers and therapeutic targets. Further research is needed to fully elucidate their mechanisms and clinical relevance in breast cancer biology.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"15 ","pages":"Article 100152"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145121121","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}

{"title":"Decoding EMT through liquid biopsy: A path to early detection and targeted therapy","authors":"Revathi Boyina ,&nbsp;Prasanna Kumar Desu ,&nbsp;Sreya Kosanam ,&nbsp;Anusha Rapuri ,&nbsp;Ramesh Alluri ,&nbsp;Jadala Shankaraswamy ,&nbsp;Sri Chandana Mavulati ,&nbsp;Vanitha Kondi","doi":"10.1016/j.adcanc.2025.100141","DOIUrl":"10.1016/j.adcanc.2025.100141","url":null,"abstract":"<div><div>Epithelial-mesenchymal transition (EMT) is a key biological process that enables cancer cells to acquire invasive, migratory, and therapy-resistant properties, driving metastasis and poor clinical outcomes. Traditional tissue biopsies, while informative, provide only static and localized snapshots of tumors, limiting their ability to capture dynamic changes like EMT. Liquid biopsy has emerged as a powerful, minimally invasive tool to monitor tumor evolution in real time by analyzing circulating tumor cells (CTCs), cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), and extracellular vesicles (EVs) from body fluids. This review highlights the molecular mechanisms that govern EMT, including transcriptional, signaling, and epigenetic regulation, and discusses how EMT-associated alterations can be detected through liquid biopsy. We explore the clinical applications of EMT monitoring via liquid biopsy for early detection of metastasis, prognostic assessment, therapy selection, and monitoring minimal residual disease (MRD). Despite current challenges such as the biological complexity of EMT, detection sensitivity, and the need for standardization, technological advances and emerging computational tools are paving the way for the integration of liquid biopsy into precision oncology. Understanding and decoding EMT through liquid biopsy represents a promising frontier for improving cancer diagnosis, prognosis, and therapeutic strategies, offering hope for more personalized and effective cancer management in the future.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"15 ","pages":"Article 100141"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329774","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}

{"title":"The effect of acute and prolonged acidosis on a panel of carcinoma cell lines","authors":"Maria Dravecka ,&nbsp;Claire Wells ,&nbsp;Ole Morten Seternes ,&nbsp;Jakob Mejlvang","doi":"10.1016/j.adcanc.2025.100157","DOIUrl":"10.1016/j.adcanc.2025.100157","url":null,"abstract":"<div><div>Due to cancer cell metabolism and disorganized tissue structure, the tumour microenvironment is associated with several pathophysiological conditions, including hypoxia, nutrient deprivation, accumulation of waste products, and acidification of the tumour microenvironment (tumour acidosis). Despite the belief that tumour acidosis drives tumorigenesis, it is still unclear how cancer cells respond to acidosis in the absence of other pathophysiological conditions. Here, we investigate how both acute and prolonged acidosis (pH 6.8) affects different epithelial features of a panel of carcinoma cell lines. We find that acute acidosis in all cell lines investigated represses cell growth and causes a disturbance of adherens junctions and apical-basal polarity, reminiscent of epithelial-to-mesenchymal transition (EMT). However, these changes did not coincide with altered expression of E− and N-cadherin. Neither did acute acidosis have a general effect on adhesion and migration in our panel of cell lines. Exposing our panel of carcinoma cell lines to acidosis for more than six weeks did not lead to adaptations restoring cell growth. On the contrary, prolonged acidosis caused one cell line (A431) to halt proliferation. Another cell line (A549) reacted to prolonged acidosis by gradually inducing the expression of ZEB2, which in turn orchestrated cadherin switching, possibly indicating a gradual induction of EMT. In the rest of the cell lines, we did not find any noticeable effect of prolonged acidosis. Lastly, all cell lines quickly restored their original phenotype and growth rate when returned to media with normal pH (pH 7.5). Collectively, our findings reveal that carcinoma cells exposed to moderate acidosis (pH 6.8) generally exhibit slower proliferation rates and a reduction in apical-basal polarity. Furthermore, we conclude that prolonged exposure to acidic conditions, depending on the specific cell line, may elicit responses that could influence tumour progression and the efficacy of cancer treatments.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"15 ","pages":"Article 100157"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145361517","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}