Cancer Cell International最新文献

{"title":"Breast neoplasm epithelial-mesenchymal transition and cytokines: a systematic review.","authors":"Yian Chen, Haining Ding, Jiaqing Song, Xiufei Gao","doi":"10.1186/s12935-025-03973-x","DOIUrl":"10.1186/s12935-025-03973-x","url":null,"abstract":"<p><p>A crucial aspect of the association involving inflammation and the development of cancer is the ability of cancer cells to undergo a transition into mesenchymal cells. The process is referred to as epithelial-mesenchymal transition (EMT). Cytokines and chemokines, which are inflammatory agents found in the carcinoma microenvironment, induce epithelial-mesenchymal transition (EMT) changes in malignant cells. Evaluating the role of cytokines in EMT in breast carcinoma and investigating their potential therapeutic implications is the objective of this comprehensive research report. The following search criteria were applied to the Cochrane, Embase, PubMed, and Web of Science databases: \"cytokines,\" \"the cytokines,\" \"chemokines,\" \"EMT,\" \"epithelial-mesenchymal transition or transformation,\" \"breast tumor,\" \"breast carcinoma,\" and \"breast cancer.\" A body of research comprising 54 articles has demonstrated that a number of cytokines, including TNF-α, TGF-β, and IL-6, contribute to the promotion of EMT alterations in breast tumors. The epithelial markers E-cadherin and β-catenin were downregulated as a consequence of morphological changes induced by EMT; conversely, the mesenchymal markers N-cadherin, vimentin, and fibronectin were upregulated. The EMT transforming factors (EMT-TF) TWIST/ZEB/SNAI1/SNAI2 were upregulated. Pharmaceuticals with the capacity to specifically target cytokines or their epithelial-mesenchymal transition (EMT) signalling pathways have the potential to significantly reduce treatment resistance, impede the progression of cancer, and prevent the recurrence of breast cancer. Epithelial-mesenchymal transition (EMT) induced by cytokines is a factor in breast cancer progression and metastasis.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"323"},"PeriodicalIF":6.0,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcription factor MYB regulates glycolysis to promote the transfer and malignant progression of gastric cancer through the SSBP2/ISL1 axis.","authors":"Zhenni Sun, Mi Zhou, Yasai Yao, Xuehong Chen, Tao Qin, Yafei Han, Lu Yue, Ruyong Yao","doi":"10.1186/s12935-025-03985-7","DOIUrl":"10.1186/s12935-025-03985-7","url":null,"abstract":"<p><strong>Background: </strong>The transcription factor (TF) MYB is crucial to many biological processes. Single-stranded DNA binding protein 2 (SSBP2), insulin gene enhancer protein 1 (ISL1) and glycolysis participated in the development of gastric cancer (GC). This study aims to explore the regulatory mechanism of the MYB/SSBP2/ISL1 axis in the development of GC.</p><p><strong>Methods: </strong>The dataset GSE65801 of cancer tissue and paracancerous tissue samples from patients with GC was used to screen differential genes, identify GC-related key TFs and the target gene of TFs, and perform expression and survival correlation analysis. Subsequently, the expression was verified in GC tissues and cells by RT-qPCR, IHC and Western blot. CCK-8, cloning, Transwell, wound healing assay, flow cytometry and Kits testing detected the effects on cells. EMSA, Yeast one-hybrid, dual-luciferase assays, ChIP-seq analysis and ChIP-PCR analysis were used to verify transcription factor binding, and pull-down assay, CO-IP, and immunofluorescence (IF) were employed to confirm interaction. MYB action was further assessed by subcutaneous tumour experiments in nude mice.</p><p><strong>Results: </strong>MYB is the key differential expression TF in GC, and SSBP2 is a key target gene of MYB. MYB had a higher expression, but SSBP2 had a lower expression in GC patients' gastric cancer tissue. SSBP2 is a direct target of MYB in GC cells. SSBP2 was transcriptionally repressed by MYB. SSBP2 further negatively regulates ISL1 expression. MYB knockdown inhibited glycolysis, proliferation, invasion, and migration abilities in GC cells both in vivo and in vitro, but it was also reversed by SSBP2 knockdown. SSBP2 overexpression inhibits glycolysis, cell proliferation, invasion and migration abilities in GC cells, but it was reversed by ISL1 overexpression.</p><p><strong>Conclusion: </strong>MYB mediates glycolysis and malignant progression in GC cells through regulation of the SSBP2/ISL1 axis.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"322"},"PeriodicalIF":6.0,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-drug pharmacotyping improves therapy prediction in pancreatic cancer organoids.","authors":"Katharina Wansch, Uwe Pelzer, François Schneider, Florian Dölvers, Anna Kühn, Mihnea P Dragomir, Jana Ihlow, Georg Hilfenhaus, Loredana Vecchione, Matthäus Felsenstein, Dou Ma, Markus Lerchbaumer, Christian Jürgensen, Marcus Bahra, Adrian E Granada, Gregor Duwe, Sebastian Stintzing, Ulrich Keilholz, Christopher C M Neumann","doi":"10.1186/s12935-025-03969-7","DOIUrl":"10.1186/s12935-025-03969-7","url":null,"abstract":"<p><p>Patient-Derived Organoids (PDOs) represent a promising technology for therapy prediction in pancreatic cancer, with the potential of enhancing treatment outcomes and allowing more effective, personalized treatment choices. However, classification approaches into sensitive and resistant models remain very variable and are based on single-agent testing only, neglecting interactive effects of multi-drug combinations. Here, we established 13 PDOs and performed both single-agent and multi-drug testing. By comparing different clustering approaches of drug-response metrics and establishing a new classification approach based on pharmacokinetic modelling, we were able to evaluate which score best predicts the clinical response of patients. Our newly developed score considered the Area Under The Curve (AUC) of cell viability curves and reached a prediction accuracy of 85%. Our data supports previous findings for PDOs to constitute an effective platform for translational drug testing. Furthermore, our results suggest that the AUC is a more accurate drug-response metric than the half maximal inhibitory concentration (IC₅₀), and that multi-drug testing yields a higher accuracy than single-agent testing. The methodology and outcomes presented in this study are of critical relevance for future PDO-based translational trials as they allow a new physiology-based approach towards multi-drug testing and classification of organoid response, which improves PDO prediction accuracy.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"321"},"PeriodicalIF":6.0,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The association between periostin and tumor microenvironment: a promising cancer prognostic biomarker and therapeutic target to combat tumor progression and chemoresistance.","authors":"Mohsen Nabi-Afjadi, Farnoosh Farzam, Sina Soltani, Nafiseh Golestani, Shiva Sarani Asl, Fatemeh Aziziyan, Hamidreza Zalpoor, Fatemeh Ghasemi, Bahareh Dabirmanesh, Khosro Khajeh","doi":"10.1186/s12935-025-03959-9","DOIUrl":"10.1186/s12935-025-03959-9","url":null,"abstract":"<p><p>Over the past few decades, cancer research has increasingly focused on tumor microenvironment (TME). The TME contains diverse cellular components and secreted factors, including leukocytes, endothelial cells, cancer-associated fibroblasts, and other non-cancerous cells and extracellular matrix proteins. The interactions between tumor cells and microenvironment elements are complex and unpredictable. Nonetheless, these relationships govern and control several cancer traits, including immune response, metastasis, differentiation status, cell proliferation, and resistance to cell death. In this line, Matricellular proteins, including periostin (POSTN), are increasingly recognized for their regulatory roles in the TME and cancer progression. Periostin is involved in tumor biology through matrix remodeling, invasion, and proliferation. In this review, we focused on the role of periostin as a biomarker for cancer growth and treatment resistance and a potential prognostic and therapeutic factor in cancer patients. In addition, we will discuss the periostin's dual role as both a promoter and inhibitor of tumor growth, depending on its concentration and cellular context. Key findings indicate that low periostin levels may suppress cancer progression by preventing epithelial-to-mesenchymal transition (EMT). In contrast, high levels can enhance migration and metastasis through the activation of integrin signaling pathways. Furthermore, we will discuss the implications of targeting periostin in therapeutic strategies, particularly in light of its complex functions within the TME.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"320"},"PeriodicalIF":6.0,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating proteomics and bioinformatics for the identification of breast cancer biomarkers interacting with telomeric G-quadruplex.","authors":"Ilaria Iacobucci, Irene Cipollone, Flora Cozzolino, Rosa Gaglione, Maria Rosaria Mentino, Chiara Platella, Domenica Musumeci, Angela Arciello, Daniela Montesarchio, Maria Monti","doi":"10.1186/s12935-025-03955-z","DOIUrl":"10.1186/s12935-025-03955-z","url":null,"abstract":"<p><p>The identification of reliable biomarkers is essential for improving breast cancer (BC) detection, prognosis, and treatment. This study explores a human telomeric G-quadruplex (G4) model, tel₄₆, functionalized on Controlled Pore Glass (CPG) support, as a novel biomarker discovery tool. The oligonucleotide tel₄₆ mimics multimeric G4 structures in telomeric overhangs. Using affinity purification-mass spectrometry, 93 proteins interacting with tel₄₆ were identified starting from nuclear extract of MCF7 cells, linking them to pathways in DNA replication, repair, and genome stability, which are frequently altered in cancer. Integrating AP-MS data with quantitative proteomics comparing MCF7 to non-tumorigenic MCF10A cells, 27 tel₄₆ interactors were identified among upregulated proteins. Functional analyses revealed enrichment in genome maintenance and repair pathways, while downregulated proteins were associated with fundamental cellular functions. Further bioinformatics analysis using public cancer proteomics database 19 were validated. Bioinformatic analysis based on transcriptomics and clinical data revealed MSH6, MSH2, ESRP1, and WDHD1 as the most promising potential biomarkers for breast cancer. Indeed, these proteins are highly expressed in BC and generally correlated to poor prognosis: in addition to their role as potential biomarkers for early diagnosis, these proteins might be used as targets for specific treatment, enhancing radiation sensitivity or decreasing tumour cell proliferation. As a proof-of-concept, this study proposes tel₄₆-functionalized CPG as a potential tool for isolating cancer-related proteins and underscores the potential of G4-interacting proteins as biomarkers for BC diagnosis and therapy. Moreover, these findings establish a basis for further research into G4-mediated cancer mechanisms.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"319"},"PeriodicalIF":6.0,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crosstalk between noncoding RNAs and autophagy in renal cell carcinoma: Deciphering molecular pathways and therapeutic prospects.","authors":"Mina Alimohammadi, Mojgan Noroozi, Alireza Mafi, Fateme Zare Khormizi, Amirhosein Abbasi, Najma Farahani, Seyedeh Mahdieh Khoshnazar, Mehrdad Hashemi, Afshin Taheriazam, Kiavash Hushmandi","doi":"10.1186/s12935-025-03957-x","DOIUrl":"10.1186/s12935-025-03957-x","url":null,"abstract":"<p><p>Renal cell carcinoma (RCC) is one of the most common and aggressive forms of kidney cancer, accounting for over 90% of cases. Despite advances in diagnosis and treatment, RCC is often detected at advanced stages and demonstrates poor response to traditional therapies such as chemotherapy, radiotherapy, and hormonal treatment. Consequently, novel molecular targets are urgently needed. Autophagy, a tightly regulated catabolic mechanism that preserves cellular homeostasis via degradation of damaged organelles and proteins, plays a dual role in RCC-acting both as a tumor suppressor in early stages and a tumor promoter under stress conditions. Recent studies have revealed that non-coding RNAs (ncRNAs), particularly long ncRNAs and microRNAs (miRNAs), are key regulators of autophagy in various cancers, including RCC. These ncRNAs influence the expression of autophagy-related genes and modulate critical signaling pathways such as PI3K/AKT/mTOR, AMPK, p53, and KEAP1/NRF2. By acting as molecular sponges, scaffolds, and transcriptional regulators, ncRNAs either enhance or suppress autophagic activity, thereby affecting tumor progression, metastasis, and treatment resistance. This review synthesizes current knowledge on the crosstalk between ncRNAs and autophagy in RCC. We identify specific ncRNAs involved in RCC pathogenesis, describe their regulatory mechanisms, and evaluate their potential as diagnostic biomarkers and therapeutic targets. Understanding these complex molecular interactions may lead to more effective, personalized treatment strategies and improved clinical outcomes for RCC patients.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"318"},"PeriodicalIF":6.0,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integration of multi-omics approaches in exploring intra-tumoral heterogeneity.","authors":"Mengmeng Dong, Liping Wang, Ning Hu, Yueli Rao, Zhen Wang, Yu Zhang","doi":"10.1186/s12935-025-03944-2","DOIUrl":"10.1186/s12935-025-03944-2","url":null,"abstract":"<p><p>Intra-tumoral heterogeneity (ITH) is common in malignant tumors and arises from dynamic variations across genetic, epigenetic, transcriptomic, proteomic, metabolic, and microenvironmental factors. This complexity drives tumor evolution and treatment resistance, undermining the accuracy of clinical diagnosis, prognosis, and treatment planning. Despite recent advances in multi-omics technologies that enable comprehensive mapping of ITH across molecular layers, major challenges remain in clinical translation. This review outlines the principles and clinical applications of eight major omics modalities in the context of ITH: genomics, single-cell genomics, transcriptomics, epigenomics, proteomics, radiomics, microbiome, and metabolomics. We highlight the unique contributions of each omics platform to tumor profiling and emphasize how their integration enhances biological interpretation, patient stratification, and biomarker discovery. Furthermore, we will focus more extensively on the limitations of applying these approaches to ITH analysis. Instead of providing an exhaustive catalog, this review highlights major controversies, technical hurdles, and conceptual gaps that impede the clinical translation of multi-omics-based ITH analysis, with the aim of addressing ITH-related clinical challenges.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"317"},"PeriodicalIF":6.0,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12395700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular analysis of androgen receptor splice variant AR-V3 reveals eminent ambiguity regarding activity and clinical utility.","authors":"Neele Wüstmann, Verena Humberg, Julia Vieler, Konstantin Seifert, Martin Bögemann, Katrin Schlack, Andres Jan Schrader, Christof Bernemann","doi":"10.1186/s12935-025-03948-y","DOIUrl":"10.1186/s12935-025-03948-y","url":null,"abstract":"<p><strong>Background: </strong>Androgen receptor (AR) splice variants (AR-Vs) have emerged as potential resistance mechanisms to AR-targeted agents (ARTAs) in prostate cancer (PC), particularly in the context of castration-resistant disease. Among them, AR-V3 has been frequently detected, yet its biological function remains unclear due to conflicting results from initial studies. This study aimed to comprehensively investigate the molecular structure, activity, and clinical relevance of AR-V3.</p><p><strong>Methods: </strong>We constructed plasmids encoding two AR-V3 isoforms-one newly identified isoform matching the human reference genome (AR-V3^ref) and the other based on the 22Rv1 cell line sequence (AR-V3^22Rv1)-and transfected them into AR-negative PC-3 cells alone or co-expressed with AR full-length (AR-FL). Localization, transcriptional activity (via luciferase assays), and RNA sequencing were performed. Protein structure modeling was conducted using AlphaFold2. Nonsense-mediated decay (NMD) was assessed through pharmacological inhibition. Clinically, AR-V3 expression in circulating tumor cells (CTCs) from 65 patients starting ARTA treatment was analyzed in relation to progression-free survival (PFS) and overall survival (OS).</p><p><strong>Results: </strong>RNA-seq of AR-FL + AR-V3 vs. AR-FL alone showed no AR-V3-specific gene expression. Structure modeling revealed poor overall prediction confidence, particularly in the N-terminal domain, with no consistent structural features differentiating AR-V3^ref and AR-V3^22Rv1. Both isoforms localized mainly to the cytoplasm, regardless of hormonal stimulation or AR-FL co-expression. Neither isoform showed androgen receptor element (ARE) binding activity unless co-expressed with AR-FL. NMD analysis indicated neither isoform was degraded by this pathway. Clinically, AR-V3 + patients had significantly shorter OS (median 13 vs. 23 months; p = 0.02) among CTC + patients but showed no difference in PSA response or PFS under ARTA treatment.</p><p><strong>Conclusions: </strong>Our data demonstrate that both AR-V3 isoforms are functionally inactive, lacking autonomous nuclear translocation or transcriptional activity. AR-V3 is not a substrate for NMD, and its protein structure remains poorly defined. While associated with worse overall survival, AR-V3 lacks predictive value for ARTA response, underscoring its limited utility as a biomarker. These findings emphasize the need for functional validation before integrating putative biomarkers into clinical practice.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"316"},"PeriodicalIF":6.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12379386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AZD5153 enhances the chemo-sensitivity of gemcitabine on pancreatic cancer cells in vitro and in vivo.","authors":"Haixin Zhu, Minmin Shen, Yiqian Zhu, Ruoqi Wang, Rong Dong, Yuyu Huang, Lulin Zhu, Ying Li, Youyou Yan, Jiang Lou, Bo Zhang, Nengming Lin, Biqin Tan","doi":"10.1186/s12935-025-03952-2","DOIUrl":"10.1186/s12935-025-03952-2","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic cancer is a malignant disease with a poor prognosis. Gemcitabine (GEM), the first-line treatment drug, shows limited efficacy because of the notorious drug resistance of pancreatic cancer. Therefore, the development of sensitive drugs for pancreatic cancer is essential. AZD5153 is a novel bivalent BET bromodomain inhibitor with multiple anti-tumor effects on malignancy. Here, we aimed to investigate the effect of AZD5153 on the GEM sensitivity in human pancreatic cancer cells.</p><p><strong>Methods: </strong>Sulforhodamine B (SRB), clone formation assays were designed to characterize the cell viability and clone formation after treatment with AZD5153 and/or GEM. DAPI staining, flow cytometry and western blotting were used to identify the cell apoptosis. RNA-seq analysis, western blotting and qPCR were also conducted to confirm the signaling pathway involved in it. Nude mice bearing PANC-1 pancreatic cancer xenograft model was conducted to confirm the combination effect of GEM and AZD5153 in vivo.</p><p><strong>Results: </strong>As a result, AZD5153 presented a strong anti-proliferation activity and exerted synergistic effects when combined with GEM in BXPC3 and PANC-1 cell lines.Meanwhile, the combination treatment also inhibited colony formation in these two cell lines. Additionally, AZD5153 combined with GEM induced cell apoptosis. Further investigations revealed that the combination of AZD5153 and GEM decreased the phosphorylation of ERK/mTOR signaling proteins, the specific chemical activators PDBu (activator of ERK) reversed the expression of c-PARP. Besides, the expression of MUC2 was remarkable decreased after combination treatment.</p><p><strong>Conclusion: </strong>In conclusion, these results suggested that AZD5153 might be an excellent GEM sensitizer in pancreatic cancer.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"315"},"PeriodicalIF":6.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12379372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COL1A1 drives tumor progression in kidney renal clear cell carcinoma by regulating EMT through the PI3K/Akt pathway.","authors":"Hainan Zhao, Ermin Wang","doi":"10.1186/s12935-025-03956-y","DOIUrl":"10.1186/s12935-025-03956-y","url":null,"abstract":"<p><p>The aggressiveness of clear cell renal cell carcinoma (KIRC) plays a crucial role in patient prognosis. This study investigated the role of COL1A1 in KIRC progression and its underlying molecular mechanisms through bioinformatics analysis, in vitro experiments, and xenograft mouse models. COL1A1 expression was significantly upregulated in KIRC and correlated with poor patient outcomes. Knockdown of COL1A1 inhibited tumor cell proliferation, migration, and invasion in both in vitro and xenograft models, as well as suppression of epithelial-mesenchymal transition (EMT). Knockdown of COL1A1 also significantly reduced the protein levels of the stemness markers OCT4 and SOX2 in KIRC cells. Additionally, COL1A1 inhibition impaired activation of the PI3K/Akt signaling pathway. These findings underscore the pivotal role of the COL1A1/PI3K/Akt axis in KIRC progression and suggest potential therapeutic strategies targeting this pathway.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"314"},"PeriodicalIF":6.0,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12376327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}