Cancer Cell International最新文献

{"title":"Actin gamma smooth muscle 2 drives proliferation, metastasis, and 5-Fluorouracil resistance in gastric cancer: insights from a Recurrence-Related Gene Signature.","authors":"Xiuli Zhang, Yining Xu, Shan Nie, Minghan Huang, Ruochen Sun, Xin Yang, Qingshui Wang, Yao Lin","doi":"10.1186/s12935-026-04312-4","DOIUrl":"https://doi.org/10.1186/s12935-026-04312-4","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer is characterized by high recurrence rates after curative treatment, significantly contributing to poor survival outcomes. Current clinicopathological parameters inadequately predict recurrence risk, highlighting the need for robust molecular signatures to guide personalized therapy.</p><p><strong>Methods: </strong>We analyzed gene expression profiles from multiple datasets to identify recurrence-associated genes in gastric cancer. A novel Recurrence-Related Gene Signature (RRGS) was constructed using LASSO regression, and its prognostic value was validated across independent cohorts. Functional validation of actin gamma smooth muscle 2 (ACTG2), which is encoded by the ACTG2 gene, was performed through in vitro knockdown experiments, zebrafish xenograft models, and chemoresistance analyses to assess its role as a key gene product in RRGS.</p><p><strong>Results: </strong>We identified 72 consistently upregulated and 1 downregulated DEG across the two datasets, which were enriched in focal adhesion, ECM-receptor interaction, and PI3K-Akt signaling. A 32-gene RRGS reliably predicted recurrence risk and correlated with immune cell infiltration patterns. Among these genes, ACTG2 emerged as a key driver of gastric cancer aggressiveness, as its silencing significantly diminished tumor cell proliferation, migration, and invasion, and increased 5-fluorouracil sensitivity both in vitro and in vivo. Elevated ACTG2 protein expression was further validated immunohistochemically in recurrent patient tumors.</p><p><strong>Conclusion: </strong>Our findings highlight RRGS may serve as a prognostic tool and indicate that ACTG2 may plays an important role in both gastric cancer progression and chemotherapy resistance. Targeting ACTG2 or its downstream pathways may offer novel therapeutic opportunities to enhance treatment efficacy for patients with gastric cancer.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fenofibrate as an anti-cancer treatment: an in vitro study on glioblastoma cells at various oxygen levels and on normal astrocytes.","authors":"Yasmine Chokry, Anne-Claire Groo, Sophie Corvaisier, Ons Ben Hadj Hassen, Isis Blanchard, Samuel Valable, Aurélie Malzert-Fréon","doi":"10.1186/s12935-026-04309-z","DOIUrl":"https://doi.org/10.1186/s12935-026-04309-z","url":null,"abstract":"<p><p>Fenofibrate, an active pharmaceutical ingredient (API) of the fibrate class approved by the U.S. Food and Drug Administration (FDA) for the treatment of hypercholesterolemia and hyperlipidemia, has emerged as a promising candidate for repurposing in cancer. Indeed, beyond its lipid-lowering effects, fenofibrate has demonstrated antitumor properties, including antiproliferative and cytotoxic effects in normoxia (21% O₂) in preclinical models of GBM. In addition, fenofibrate may inhibit hypoxia-inducible factor-1 alpha (HIF-1α) and reduce the expression of hypoxia-inducible genes, potentially overcoming hypoxia-induced chemoresistance. These findings, combined with its established clinical safety profile, support further investigation of fenofibrate as a potential therapeutic strategy in GBM. On this basis, physico-chemical characterization of fenofibrate was assessed to determine its ability to cross the blood-brain barrier. We determined in vitro on GBM cell lines U251-MG, U87-MG and GL261, the efficacy of fenofibrate in decreasing GBM cell viability and proliferation under normoxia (21% O₂) and hypoxia (1% and 0.2% O₂). We investigated the kinetics of its internalization by HPLC. In addition, the safety of fenofibrate was evaluated on non-tumoral brain cells. Dunn's post-hoc test was used after a significant Kruskal-Wallis. Being practically insoluble in water, fenofibrate was dissolved in dimethyl sulfoxide (DMSO) for studies. Primary astrocytes showed no signs of toxicity following treatment with fenofibrate. The effect of fenofibrate on GBM cell lines was studied at various time points and exhibited a cell type-, time- and concentration-dependent cytotoxicity with an LC₅₀ of 25, 43.7 and 49.6 µM for U251-MG, U87-MG and GL261 cells, respectively. Interestingly, fenofibrate uptake was confirmed, 12.9 ± 5.7% and 14.2 ± 6.6% of fenofibrate was found in U251-MG and U87-MG cells, respectively. Intracellular concentrations of fenofibrate increased over time and no precipitation was observed. In hypoxia (1% and 0.2% of O₂), the cytotoxic effect of fenofibrate was still present, albeit decreased. Furthermore, fenofibrate induced a cytostatic effect on U251-MG and U87-MG under both normoxia (21% O₂) and hypoxia (1% and 0.2% O₂), reducing their proliferation. Under the experimental conditions tested, namely in vitro studies, fenofibrate appeared more efficient compared with temozolomide, the standard treatment for GBM. This study demonstrated the cytotoxic and cytostatic effect of fenofibrate on GBM cells. These results indicate that fenofibrate may be a therapeutic alternative for GBM treatment.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction Note: MicroRNA-214-3p inhibits proliferation and cell cycle progression by targeting MELK in hepatocellular carcinoma and correlates cancer prognosis.","authors":"Yue Li, You Li, Yao Chen, Qian Xie, Ningning Dong, Yanjun Gao, Huan Deng, Chunhua Lu, Suihai Wang","doi":"10.1186/s12935-026-04327-x","DOIUrl":"https://doi.org/10.1186/s12935-026-04327-x","url":null,"abstract":"","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"26 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13130598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811503","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":"Decoding notch signaling pathway: an updated insight into its role in colorectal cancer progression and therapy.","authors":"Mehran Molavand, Azita Asadi, Maryam Majidinia, Bahman Yousefi","doi":"10.1186/s12935-026-04298-z","DOIUrl":"https://doi.org/10.1186/s12935-026-04298-z","url":null,"abstract":"<p><p>Colorectal cancer (CRC) represents a major global health challenge, marked by a high mortality rate and a strong association with aging. A key factor contributing to the progression of this malignancy is the overactivation of oncogenic signaling pathways. Notch signaling is a conversed pathway. This pathway utilizes a distinct mechanism that relies on direct cell-to-cell interactions for activation. Notch signaling ligands and receptors possess unique biological functions and distinct structures. Aberrant Notch signaling plays a pivotal role in CRC progression. It coordinates diverse oncogenic programs, including sustained proliferative signaling, invasive behavior, cancer stem cell maintenance, acquisition of therapeutic resistance, and the promotion of angiogenesis through increased microvascular density. The interplay between Notch signaling and other oncogenic pathways leads to the development of CRC. Designing therapeutic agents that target the Notch pathway is a feasible strategy to mitigate the oncogenic features associated with CRC progression. Furthermore, assessing the components of this pathway can serve as a diagnostic biomarker and offer insights into patient prognosis. Predicting the response to treatment is another clinical application of Notch evaluation. This review delves into the multi-layered roles of Notch signaling in CRC.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artesunate directly targeting MMP9 to reduce angiogenesis and increase CD8 + T cell infiltration inhibits hepatocellular carcinoma.","authors":"Ning Wang, Liang Yao, Xiaoying Dong, Xiaoqian Man, Bo Liu, Huiling Li, Jie Sun, Rujiao Jiang, Meihua Guo, Jianlei Bi, Aiguo Wang","doi":"10.1186/s12935-026-04323-1","DOIUrl":"https://doi.org/10.1186/s12935-026-04323-1","url":null,"abstract":"<p><strong>Background: </strong>Artesunate (ART) is one of the semi-synthetic derivatives of artemisinin. It is currently mainly used in the clinic for the rescue of cerebral malaria and various critical malaria. Recent studies have shown that it has a wide range of anti-tumor effects. However, its treatment for hepatocellular carcinoma (HCC) and its specific mechanism remain unclear.</p><p><strong>Purpose: </strong>This study aims to investigate ART therapeutic effects on HCC and elucidate its molecular mechanisms.</p><p><strong>Methods: </strong>This study explored the inhibitory effect of ART on HCC through in vivo and in vitro experiments. Cellular experiments evaluated the effects of ART on HCC cell lines (HepG2, H22, Hepa1-6) using CCK-8, Annexin/PI staining, wound healing, and Immunofluorescence. In vivo, ART was tested in HepG2 xenografts and H-ras12V transgenic mice, with tumor growth monitored by Doppler ultrasound. Multi-omics (transcriptomics, network pharmacology, single-cell sequencing) identified MMP9 as a key target. Mechanisms were explored via molecular docking/dynamics, thermal shift assays, and Western blot analysis. Flow cytometry and immunofluorescence confirm CD8 + T cell infiltration.</p><p><strong>Results: </strong>ART inhibited the proliferation of HCC cell lines and promoted its apoptosis. In vivo experiments showed that it had a certain inhibitory effect on the development of immune-deficient mice transplanted tumors. Continuous monitoring of tumor growth by Doppler ultrasound found that its effect was more obvious in the immune-competent spontaneous H-ras12V mouse model of liver cancer, especially for the development of small tumors. Mechanistically, ART can inhibit tumor growth by inhibiting the classic PI3K-AKT signaling pathway, which is consistent with the results in other tumor studies. At the same time, ART can directly target MMP9 and promote its degradation, thereby inhibiting tumor's angiogenesis. To explain why its effect was more pronounced in immune-competent mice, we found ART can significantly increase the tumor infiltration of CD8 + T cells and its effect is also achieved by degrading MMP9.</p><p><strong>Conclusion: </strong>Our findings reveal that ART inhibits HCC tumorigenesis and progression by targeting MMP9 to suppress angiogenesis and enhance CD8⁺ T cell infiltration. This study provides a mechanistic basis for the potential clinical application of ART in HCC therapy and identifies MMP9 as a promising therapeutic target.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"C-MYC as a key effector of WNT, PI3K/AKT, MAPK, and TGF-β signaling pathways in regulation of epithelial-mesenchymal transition during tumor metastasis.","authors":"Meysam Moghbeli","doi":"10.1186/s12935-026-04311-5","DOIUrl":"https://doi.org/10.1186/s12935-026-04311-5","url":null,"abstract":"<p><p>Epithelial-mesenchymal transition (EMT) is a key cellular process that facilitates distant metastasis during tumor progression. Tumor cells lose their epithelial characteristics while obtaining mesenchymal features during EMT process. This process is associated with a complex interaction between tumor cells, microenvironment, and signaling pathways. Therefore, it is helpful to clarify the molecular mechanisms of EMT process to introduce novel diagnostic and therapeutic markers to target malignant tumor cells. C-MYC is a transcription factor that regulates cell proliferation, apoptosis, metabolism, and EMT process. C-MYC is an effector of various signaling pathways that regulates EMT process during tumor progression. Therefore, in the present review we discussed the role of signaling pathways in regulation of C-MYC mediated EMT process during tumor progression. It has been shown that WNT, MAPK, TGF-β, and PI3K/AKT pathways are the main regulators of C-MYC mediated EMT process in tumor cells. This review paves the way to introduce C-MYC as a reliable therapeutic target to reduce metastatic ability of tumor cells.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147762717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The mechanistic role of the thromboxane A2 receptor (TBXA2R) in non-small cell lung cancer (NSCLC).","authors":"Qiushi Wang, Asad Khan, Tianshun Zhang","doi":"10.1186/s12935-026-04283-6","DOIUrl":"https://doi.org/10.1186/s12935-026-04283-6","url":null,"abstract":"","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147762976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovative approaches in the treatment of hematologic malignancies: the role of CRISPR-engineered microbiomes along the gut-immune axis in immunotherapy development.","authors":"Chou-Yi Hsu, Amr Ali Mohamed Abdelgawwad El-Sehrawy, Samer Saleem Alshkarchy, Amir S Abdul, Subbulakshmi Ganesan, Piyush Kumar Gupta, Renu Sharma, Priya Priyadarshini Nayak, Amirali Ebrahimpour, Yeganeh Khazaei","doi":"10.1186/s12935-026-04316-0","DOIUrl":"https://doi.org/10.1186/s12935-026-04316-0","url":null,"abstract":"","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147762970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insulin-like growth factor-binding protein 5 promotes prostate cancer metastasis and osteoblastic activity by inducing chemokines and activating NF-κB signaling.","authors":"Zhongqin Gong, Changmin Lin, Jia Peng, Xin Liu, Chao Tian, Junfang Zhang, Wenjie Dai, Qinqin Tao, Shanqiang Zhang, Chongwei Xie","doi":"10.1186/s12935-026-04317-z","DOIUrl":"https://doi.org/10.1186/s12935-026-04317-z","url":null,"abstract":"","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147762967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hsa_circ_0007158 promotes colorectal cancer progression via the ceRNA axis and its association with immune infiltration.","authors":"Guida Fang, Lei Qiu, Dalai Xu, Feng Lu, Tao Zhang, Gengji Wu, Xuzhu Gao, Gang Wang, Yongchang Miao","doi":"10.1186/s12935-026-04313-3","DOIUrl":"https://doi.org/10.1186/s12935-026-04313-3","url":null,"abstract":"","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147762696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}