Neoplasma最新文献

{"title":"BATF2 reverses multidrug resistance of gastric cancer cells and centrosome clustering by suppressing ATM phosphorylation.","authors":"Wei Yang, Jianlin Song, Lixia Jiang, Wenchuan Zhu, Jianxun Wang, Qi Huang, Jiawei Hu, Rong Zeng, Bian Wu","doi":"10.4149/neo_2026_251127N498","DOIUrl":"https://doi.org/10.4149/neo_2026_251127N498","url":null,"abstract":"<p><p>Chromosome instability (CIN) is a major contributor to drug resistance and recurrence. As a crucial mechanism of CIN, centrosome clustering has emerged as a promising therapeutic strategy. However, the roles and regulatory mechanisms of centrosome clustering in gastric cancer remain unclear. BATF2 was previously identified as a key modulator of multidrug resistance (MDR) in gastric cancer (GC). To examine the involvement of centrosome clustering in the mechanism by which BATF2 reverses MDR in GC, adriamycin (ADR)- and vincristine (VCR)-resistant cell lines, NCI-N87/ADR and NCI-N87/VCR, were used for investigations. Expression of BATF2 was downregulated in both drug-resistant cells, particularly in NCI-N87/ADR cells. Cells with BATF2 knockdown exhibited higher cell viability and lower apoptosis rates, and such changes were reversed by BATF2 overexpression. The enhanced centrosome clustering in cells transfected with sh-BATF2 was accompanied by increased KIFC1 expression, which was inhibited after BATF2 overexpression. BATF2 reversed MDR and inhibited centrosome clustering by inhibiting ATM phosphorylation, which was evidenced by ATM overexpression. Meanwhile, KU-60019, a specific inhibitor of ATM, could markedly reverse the pro-tumor effects of BATF2 knockdown. In conclusion, BATF2 is a potential target for reversing MDR in GC, and targeting KIFC1-related centrosome clustering by suppressing ATM phosphorylation is proposed as a key mechanism.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"V9302, an inhibitor of glutamine transport, suppresses proliferation and migration, and induces apoptosis in non-small cell lung cancer cells through ROS-mediated mTOR/p70S6K pathway.","authors":"Shuo Li, Xingyu Zhang, Teng Chen, Xiaofan Cong, Wenjing Feng, Xiaojin Sun, Cheng Zha, Surong Zhao, Pei Zhang","doi":"10.4149/neo_2026_251028N451","DOIUrl":"https://doi.org/10.4149/neo_2026_251028N451","url":null,"abstract":"<p><p>This study aimed to investigate the effects and underlying mechanisms of V9302, an inhibitor of glutamine transport, on non-small cell lung cancer (NSCLC) cells. Proliferation was assessed using the cell counting kit-8, colony formation, and EdU assays. Mitochondrial membrane potential was evaluated through JC-1 staining. Cell cycle distribution, apoptosis, and reactive oxygen species (ROS) levels were analyzed by flow cytometry, while migration was assessed using wound healing and Transwell assays. Western blotting was performed to determine protein expression levels. The antitumor efficacy of V9302 in vivo was evaluated using a xenograft mouse model with PC-9 cells. The results demonstrated that V9302 inhibited cell proliferation and induced G1-phase arrest in human lung adenocarcinoma PC-9 and A549 cells. Western blotting showed that V9302 significantly inhibited the ASCT2 protein expression in both PC-9 and A549 cells. Additionally, V9302 promoted apoptosis through a mitochondrial-dependent pathway, as evidenced by elevated levels of cleaved PARP, cleaved Caspase 3, cleaved Caspase 9, and Bax. V9302 also suppressed cell migration by downregulating N-cadherin and vimentin expression. Notably, V9302 triggered significant ROS accumulation and inhibited mTOR/p70S6K pathway activation, an effect that was partially restored by N-acetylcysteine, a ROS scavenger. Pretreatment with mTOR activator MHY1485 mitigated the inhibitory effects of V9302 on cell proliferation and migration, as well as its induction of apoptosis. Furthermore, V9302 inhibited tumor growth and induced apoptosis in a xenograft mouse model, without inducing detectable visceral toxicity. In conclusion, these findings demonstrate that V9302 reduces cell proliferation and migration, and causes apoptosis through the ROS-mediated mTOR/p70S6K pathway in NSCLC cells. These findings provide a novel theoretical foundation for advancing both academic and clinical research on NSCLC treatment.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic model based on mitochondrial genes highlights ABCD3 as a potential therapeutic target in colorectal cancer.","authors":"Shuyu Chen, Youyue Li, Wenbo Ding, Yujuan Yin, Xiaoqi Xin, Xueyang Wei, Siqi Bao, Bei Pan, Huiling Sun, Mu Xu","doi":"10.4149/neo_2026_250916N395","DOIUrl":"https://doi.org/10.4149/neo_2026_250916N395","url":null,"abstract":"<p><p>Studies have shown that abnormal mitochondrial function is closely associated with the development and progression of colorectal cancer (CRC); however, prognostic models based on mitochondria-related genes are still lacking. We systematically analyzed the expression of mitochondrial-related genes in CRC patients and constructed and validated a mitochondrial gene risk prognostic model using various bioinformatics methods across the TCGA and GEO databases. We also investigated the effects of tumor microenvironment, immune cell infiltration, tumor mutation load, and drug sensitivity on patient prognosis. In addition, we overexpressed the ABCD3 gene using CRISPR-dCas9 technology and further explored the role of ABCD3 in cell proliferation and apoptosis by protein blotting and flow cytometry. The mitochondrial gene risk model was effective in predicting the prognosis of CRC patients, which showed that the high-risk group was significantly different from the low-risk group in terms of immune cell infiltration. Further analyses revealed a strong association between risk scores and clinicopathological features, immune infiltration, and drug sensitivity. We constructed a prognostic prediction model based on mitochondria-related genes and found that ABCD3 provides a novel biomarker for the individualized treatment of CRC.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isoguanosine exerts anticancer effects in Huh-7 cells by modulating ROS-dependent MAPK and AKT signaling.","authors":"An-Qi Wang, Xiao-Yu Jin, Ying-Hua Luo, Nan Wu, Yan-Jun Tang, Yan-Zhi Liu, Tian-Zhu Li, Cheng-Hao Jin","doi":"10.4149/neo_2026_251204N508","DOIUrl":"https://doi.org/10.4149/neo_2026_251204N508","url":null,"abstract":"<p><p>Isoguanosine (ISO) is a naturally occurring bioactive compound with multiple pharmacological properties. In this study, the inhibitory effects of ISO on hepatocellular carcinoma (HCC) cells and its underlying molecular mechanisms were investigated. The cell viability after ISO treatment was assessed using the CCK-8 assay, trypan blue staining, and Hoechst 33342/PI double staining. The relevant targets of ISO and their regulatory mechanisms were predicted using network pharmacology and molecular docking technology. The induction of apoptosis by ISO on Huh-7 cells was detected by Annexin V-FITC/PI double staining combined with flow cytometry and western blotting. The cell cycle arrest effect of ISO on Huh-7 cells was detected by Ki-67 staining, flow cytometry, and western blotting. The migration-inhibition effect of ISO on Huh-7 cells was detected by the wound healing, Transwell, and western blotting. In addition, the effects of reactive oxygen species (ROS) and protein kinase B (AKT) on Huh-7 cells were investigated by using N-acetyl cysteine (NAC) and AKT inhibitor HY10249, respectively. Cell viability assays demonstrated that ISO exerts a significant cytotoxic effect on HCC cell lines. Network pharmacology analysis revealed that the core targets of ISO are associated with ROS, AKT, and mitogen-activated protein kinase (MAPK) signaling pathways. Molecular docking results indicate that ISO has a strong binding affinity for AKT1, CASP3, and GSK3B. Apoptosis assays indicated that ISO induces apoptosis in Huh-7 cells via the mitochondria-dependent pathway. Furthermore, ISO modulates apoptosis through the MAPK and signal transducer and activator of transcription 3 (STAT3) signaling pathways. Cell cycle assays showed that ISO induces G2/M phase arrest by elevating intracellular ROS levels. Migration assays demonstrated that ISO inhibits cell migration by regulating the AKT signaling pathway. In addition, pretreatment with NAC reversed ISO-induced apoptosis, cell cycle arrest, and inhibition of migration. ISO promotes apoptosis, induces cell cycle arrest, and inhibits Huh-7 cell migration. These findings provide a theoretical basis for further pharmacological research and support the potential development and application of ISO as an anticancer agent.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"(-)-Guaiol inhibits lung cancer via PPARG-dependent fatty acid oxidation.","authors":"Zhen-Yu Zhao, Bo Zhang, Ying-Bin Luo, Xing-Yu Wang, Yu-Li Wang, Xi Wang, Jian-Hui Tian, Jian-Chun Wu, Yan Li","doi":"10.4149/neo_2026_251111N475","DOIUrl":"10.4149/neo_2026_251111N475","url":null,"abstract":"<p><p>The objective of this study was to explore the effect of (-)-guaiol on lung cancer using experimental validation, mRNA sequencing, and network pharmacology. Potential targets of (-)-guaiol and lung cancer were identified through SwissTargetPrediction, TCMSP, PharmMapper, OMIM, GeneCards, and DisGeNET databases. Common targets were analyzed using PPI network, topological screening, and functional enrichment using STRING, Cytoscape, and Metascape. Molecular docking with core targets was performed, along with molecular dynamics. In vitro assays (cell counting kit-8 assay, colony formation, wound healing, Transwell, western blot) and in vivo studies (subcutaneous xenograft modeling in nude mice, immunohistochemistry, mRNA sequencing) were conducted to validate the anti-tumor effects and mechanisms of (-)-guaiol compared with the control group. Through multi-database prediction, 153 (-)-guaiol targets and 91 common lung cancer targets were identified. Protein-protein interaction (PPI) network analysis screened 21 core targets (including ESR1, EGFR, etc.). GO and KEGG enrichment analyses revealed that these targets are involved in the regulation of pathways such as fatty acid metabolism. Molecular docking and molecular dynamics results demonstrated that (-)-guaiol possessed a favorable binding affinity toward the target proteins SRC, PTGS2, GSK3B, PPARG, ESR1, and HSP90AA1. mRNA sequencing indicated that the gene expression levels of both PPARG and CD36 were downregulated in lung cancer tissues of mice treated with (-)-guaiol compared with the control group. Combining the results of molecular docking, molecular dynamics, and mRNA sequencing, we selected the PPARG-related signaling pathway for subsequent experiments. Both in vivo and in vitro experiments validated that (-)-guaiol inhibits lung cancer cell proliferation, invasion, and xenograft tumor growth in mice by downregulating the PPARG pathway. To conclude, our results demonstrated that (-)-guaiol suppresses lung cancer progression through downregulation of the fatty acid oxidation-related pathway mediated by PPARG.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":" ","pages":"88-102"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression and prognostic significance of CD66b in diffuse large B-cell lymphoma.","authors":"Yun Tao, Yaxun Wu, Xingsong Zhang, Song He, Xiaobing Miao","doi":"10.4149/neo_2026_251014N432","DOIUrl":"https://doi.org/10.4149/neo_2026_251014N432","url":null,"abstract":"<p><p>Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma in the world. It exhibits high heterogeneity and invasiveness and is prone to developing treatment resistance. Therefore, there is an urgent need for good prognostic evaluation indicators and therapeutic targets. In recent years, immunotherapy has become a research hotspot for DLBCL. Tumor-associated neutrophil (TAN) is widely expressed in various tumors and is an important component of the immune microenvironment. However, there have been few studies on the role of TAN in DLBCL. This study has demonstrated that CD66b, which is a marker of TAN, is a good prognostic marker of DLBCL and its expression is related to the prognosis of DLBCL patients. The expression level of CD66b is also closely correlated with the objective response rate of the R-CHOP treatment regimen in DLBCL patients with non-GCB subtype. The expression level of CD66b has a high reference value for the determination of the treatment plan. The combined detection of CD66b and PD-L1/PD-L2 is of significance to predict the prognosis of DLBCL patients.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"73 2","pages":"146-154"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"circRNA circ-ZEB1 promotes gallbladder carcinomas progression by regulating the miR-144-3p/ZEB2 axis.","authors":"Luoshun Huang, Yang Zhang, Fan Yang, Yisheng Ling, Xianfei Zhou","doi":"10.4149/neo_2026_251124N495","DOIUrl":"https://doi.org/10.4149/neo_2026_251124N495","url":null,"abstract":"<p><p>Gallbladder cancer (GBC) is the most common and aggressive type of tumor occurring in the biliary system. Several studies have indicated the possible functions of circular RNAs (circRNAs) in GBC tumorigenesis. This research aimed to explore the roles of a novel circRNA, circ-ZEB1 (hsa_circ_0093509), in GBC. The expressions of circ-ZEB1, miR-144-3p, and ZEB2 in GBC cells were detected using RT-qPCR or western blot. The subcellular localization of circ-ZEB1 in GBC cells was determined. The function of circ-ZEB1, miR-144-3p, and ZEB2 in GBC cells was assessed by using CCK-8, EdU staining, colony formation, or Transwell assays. The relationship among miR-144-3p and corresponding targets, circ-ZEB1 and ZEB2, was confirmed. Additionally, xenograft experiments were conducted to assess the role of circ-ZEB1 in tumor growth in vivo. circ-ZEB1 was predominantly found in the cytoplasmic region of GBC cells and was upregulated in the GBC cell lines. Suppression of circ-ZEB1 reduced the proliferation and migration of GBC-SD and SGC-996 cells. Knockdown of circ-ZEB1 attenuates tumor growth in vivo. Mechanistically, circ-ZEB1 sponged miR-144-3p, which targeted ZEB2. Additionally, inhibition of miR-144-3p rescues the effects of circ-ZEB1 or ZEB2 knockdown. These results clarified a vital role of the circ-ZEB1/miR-144-3p/ZEB2 axis in GBC advancement, and may serve as a novel therapeutic target for GBC treatment.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"73 2","pages":"133-145"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell surface topography differs in the human \"glia-like\" and glioma cultures.","authors":"Ivana Sivakova, Maria Lorencova, Anna Perzelova, Paulina Galfiova, Stefan Polak","doi":"10.4149/neo_2026_250623N278","DOIUrl":"10.4149/neo_2026_250623N278","url":null,"abstract":"<p><p>Glioblastoma multiforme is the most malignant and incurable primary brain tumor. Infiltrative growth of gliomas into surrounding brain tissue may cause the presence of normal cells in glioma cultures. The aim of this study is to develop a simple, rapid method for detecting normal cells in short-term glioma cultures, to be applied primarily to personalized glioma treatment. Cell lines with permanent cell growth consist solely of cancer cells. Here, we examined two glioblastoma cell lines (8-MG-BA and 170-MG-BA), one brain metastatic carcinoma cell line (135-BCA), five short-term glioblastomas, and five human \"glia-like\" cultures using scanning electron microscopy (SEM), standard phase contrast microscopy, and GFAP immunofluorescence. All cells in glioblastoma and carcinoma cell lines were covered with microvilli of varying density, 4/5 of short-term glioblastoma cultures contained 1-3% cells with sparse microvilli, and one culture (139-GBM) showed microvilli in 15-20% of the cells and a higher percentage of GFAP-positive cells. A rare occurrence (less than 1%) of cells bearing microvilli was observed in all \"glia-like\" cultures. Using SEM, we observed similar cells with microvilli in both glioblastoma cell lines, but in the 135-BCA line, the microvilli were significantly shorter. Microvilli rarely occurred on normal \"glia-like\" cells. Based on this observation, we conclude that our 4/5 of short-term glioblastoma cultures contain predominantly normal \"glia-like\" cells. SEM could be a valuable method for distinguishing normal and tumor cells in short-term glioblastoma cultures, which have similar morphologies at light microscopy and immunophenotypes. We conclude that microvilli are characteristic of a specific tumor cell surface topography compared to \"glia-like\" cells.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":" ","pages":"103-109"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146220531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"YBX1 promotes the stemness and metastasis of NSCLC cells by promoting CDCA8 expression.","authors":"Xiaomin Wu, Yuyou Hu, Xiuyu Ji, Yi Zhao","doi":"10.4149/neo_2026_250911N384","DOIUrl":"https://doi.org/10.4149/neo_2026_250911N384","url":null,"abstract":"<p><p>Cancer stemness is a major therapeutic challenge in oncology. This study investigated the functional role and molecular mechanism of cell division cycle-associated 8 (CDCA8) in non-small cell lung cancer (NSCLC) stem cells. In this study, NSCLC and paracancerous tissues were collected. The lung adenocarcinoma cell line A549 and the lung squamous cell carcinoma cell line NCI-H520 were used. The stem-like cell population in A549 and NCI-H520 was isolated by CD44+ fluorescence-activated cell sorting. Gene expression was detected by quantitative real-time PCR, western blotting, and immunohistochemical staining. Cell stemness was assessed by biomarker (SOX and NANOG) expression detection, colony formation assay, and sphere-formation assay. Cell migration and invasion ability were determined by the Transwell experiment. Our results showed that CDCA8 expression was higher in NSCLC tissues than in paracancerous tissues. CDCA8 overexpression enhanced stemness properties, as evidenced by increased biomarker expression and colony formation, larger sphere size, and enhanced migratory/invasive capacity. Conversely, CDCA8 knockdown had the opposite effect. Mechanistically, we identified Y-box binding protein 1 (YBX1) as a direct binding protein of CDCA8 mRNA that positively regulated CDCA8 expression. YBX1 overexpression had a similar effect to CDCA8. Furthermore, recovery experiments revealed that the stemness-promoting effect of YBX1 was reversed by CDCA8 knockdown. These findings were further validated in xenograft models, confirming that the YBX1/CDCA8 axis promoted tumorigenesis in vivo. Collectively, our study reveals that YBX1 enhances cell stemness and metastasis of NSCLC by promoting CDCA8 expression. Our findings established a new mechanism that maintains NSCLC stemness and may provide novel biomarkers.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"73 2","pages":"123-132"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CDH17 facilitates β-catenin nuclear translocation to reduce drug sensitivity in cisplatin-resistant gastric cancer cells.","authors":"Meng Liu, Zheng Han, Ziqiang Zhong, Jie Tan, Qingxi Zhu, Wei Chen, Shasha Huang, Xiaoli Chen, Xia Tian","doi":"10.4149/neo_2026_251103N459","DOIUrl":"10.4149/neo_2026_251103N459","url":null,"abstract":"<p><p>Chemoresistance greatly impairs the effectiveness of chemotherapy in gastric cancer (GC) patients. According to our prior results, Cadherin-17 (CDH17) contributes to chemoresistance in GC through activating the Wnt/β-catenin pathway; however, its specific molecular mechanisms require further elucidation. We compared the Wnt/β-catenin pathway activation levels between cisplatin (DDP)-resistant GC cell lines and their parental cell lines. Subsequently, we carried out loss-of-function and gain-of-function tests to investigate CDH17 for its effect on regulating β-catenin expression, nuclear transport, as well as transcriptional activity within DDP-resistant GC cells. Additionally, CDH17 was examined for its role in the expression of four ABC transporters using molecular assays. Finally, rescue experiments were carried out using the Wnt signaling pathway agonist CP21R7 and inhibitor IWR-1 to elucidate the specific mechanism of CDH17 in promoting chemotherapy resistance of GC cells. The results showed that the activation level of the Wnt/β-catenin signaling pathway was significantly elevated in DDP-resistant GC cell lines compared to their parental cell lines. Silencing CDH17 resulted in reduced expression, impaired nuclear translocation, and decreased transcriptional activity of β-catenin, whereas overexpression of CDH17 had the opposite effects. Notably, CDH17 was shown to specifically regulate the expression of ABCB1 (protein name: P-glycoprotein, P-gp) in resistant cells, with no observable impact on the other three ABC transporters (ABCC1, ABCG2, and ABCC2) examined. Importantly, treatment with IWR-1 effectively reversed the enhancing effect of CDH17 overexpression on P-gp protein expression, as well as its suppressive effects on DDP accumulation and chemosensitivity. Conversely, administration of CP21R7 attenuated the inhibitory consequences of CDH17 silencing on P-gp expression, DDP efflux, and drug resistance. In conclusion, CDH17 promotes the expression and nuclear translocation of β-catenin in GC cells, leading to activation of the Wnt/β-catenin signaling pathway, which subsequently upregulates ABCB1/P-gp expression and enhances cellular capacity for DDP efflux. These findings imply that targeting CDH17 could be a potential strategy for overcoming chemotherapy resistance in GC.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":" ","pages":"110-122"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}