Cancer Biology & Therapy最新文献_第5页

SLX1 silencing overcomes Olaparib resistance in metastatic castration-resistant prostate cancer by disrupting SLX4-mediated DNA repair complexes. SLX1沉默通过破坏slx4介导的DNA修复复合物来克服转移性去势抵抗性前列腺癌的奥拉帕尼耐药性。

IF 4.6 4区医学

Cancer Biology & Therapy Pub Date : 2025-12-01 Epub Date: 2025-08-11 DOI: 10.1080/15384047.2025.2545062

Xin Zhao, Shiyun Feng, Xiaoping Nitie, Shibu Muluo, Yi Lei

{"title":"SLX1 silencing overcomes Olaparib resistance in metastatic castration-resistant prostate cancer by disrupting SLX4-mediated DNA repair complexes.","authors":"Xin Zhao, Shiyun Feng, Xiaoping Nitie, Shibu Muluo, Yi Lei","doi":"10.1080/15384047.2025.2545062","DOIUrl":"10.1080/15384047.2025.2545062","url":null,"abstract":"Purpose: Metastatic castration-resistant prostate cancer (mCRPC) remains a significant therapeutic challenge and a leading cause of cancer-related mortality in men. PARP inhibitors like Olaparib are effective in homologous recombination repair (HRR)-deficient tumors, but resistance often arises through DNA repair restoration. This study explores the role of the structure-specific endonuclease subunit SLX1, a catalytic subunit of the SLX1-SLX4 endonuclease complex, in Olaparib resistance.Methods: Data from The Cancer Genome Atlas (TCGA) were used for expression and survival analyses. The CRPC cell line DU145, which harbors BRCA1 and BRCA2 mutations, was used as a cell model for both in vitro and in vivo studies.Results: Elevated SLX1A expression in prostate cancer tissues was associated with significantly reduced progression-free and overall survival. SLX1 protein was upregulated in androgen-resistant prostate cancer cell lines (DU145, 22RV1, PC3) and further increased in Olaparib-resistant DU145 (DU145-OR) cells. Silencing SLX1 via shRNA enhanced Olaparib sensitivity, reducing colony formation and increasing DNA damage and apoptosis in DU145 and DU145-OR cells. Mechanistically, SLX1 knockdown disrupted SLX4 interactions with critical DNA repair proteins (ERCC1-XPF, PLK1, and TOPBP1), impairing DNA repair complex stability. In vivo, SLX1-silenced DU145 xenografts treated with Olaparib showed significantly reduced tumor growth with decreased Ki-67 expression and increased apoptosis/necrosis compared to controls.Conclusion: This study highlights SLX1 as both a prognostic marker and potential therapeutic target to enhance PARPi efficacy in advanced prostate cancer. Targeting SLX1 may be a promising strategy to overcome Olaparib resistance in mCRPC patients with homologous recombination deficiency.","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2545062"},"PeriodicalIF":4.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Knockdown of NDUFAF6 inhibits breast cancer progression via promoting mitophagy and apoptosis. NDUFAF6的下调通过促进线粒体自噬和细胞凋亡抑制乳腺癌的进展。

IF 4.4 4区医学

Cancer Biology & Therapy Pub Date : 2025-12-01 Epub Date: 2024-12-20 DOI: 10.1080/15384047.2024.2445220

Shang Wu, Xindi Ma, Xiangmei Zhang, Kaiye Du, Chao Shi, Ahmed Ali Almaamari, Boye Han, Suwen Su, Yunjiang Liu

{"title":"Knockdown of NDUFAF6 inhibits breast cancer progression via promoting mitophagy and apoptosis.","authors":"Shang Wu, Xindi Ma, Xiangmei Zhang, Kaiye Du, Chao Shi, Ahmed Ali Almaamari, Boye Han, Suwen Su, Yunjiang Liu","doi":"10.1080/15384047.2024.2445220","DOIUrl":"https://doi.org/10.1080/15384047.2024.2445220","url":null,"abstract":"Background: While NDUFAF6 is implicated in breast cancer, its specific role remains unclear.Methods: The expression levels and prognostic significance of NDUFAF6 in breast cancer were assessed using The Cancer Genome Atlas, Gene Expression Omnibus, Kaplan-Meier plotter and cBio-Portal databases. We knocked down NDUFAF6 in breast cancer cells using small interfering RNA and investigated its effects on cell proliferation and migration ability. We performed gene expression analysis and validated key findings using protein analysis. We also assessed mitochondrial activity and cellular metabolism.Results: NDUFAF6 was highly expressed in breast cancer, which was associated with a poorer prognosis. Knockdown of NDUFAF6 reduced the proliferation and migration ability of breast cancer cells. Transcriptome analysis revealed 2,101 differentially expressed genes enriched in apoptosis and mitochondrial signaling pathways. Western blot results showed NDUFAF6 knockdown enhanced apoptosis. In addition, differential gene enrichment analysis was related to mitochondrial signaling pathways, and western blot results verified that mitophagy was enhanced in NDUFAF6 knockdown breast cancer cells. JC-1 assay also showed that mitochondrial dysfunction and reactive oxygen species content were increased after knocking down NDUFAF6. In addition, basal and maximal mitochondrial oxygen consumption decreased, and intracellular glycogen content increased.Conclusions: Knockdown of NDUFAF6 resulted in apoptosis and mitophagy in breast cancer cells and NDUFAF6 may be a potential molecular target for breast cancer therapy.","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2445220"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871497","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}

引用次数: 0

The RNA-binding protein ELAVL1 promotes Beclin1-mediated cellular autophagy and thus endometrial cancer development by affecting LncRNA-neat stability. rna结合蛋白ELAVL1通过影响LncRNA-neat的稳定性，促进beclin1介导的细胞自噬，从而促进子宫内膜癌的发生。

IF 4.4 4区医学

Cancer Biology & Therapy Pub Date : 2025-12-01 Epub Date: 2025-02-28 DOI: 10.1080/15384047.2025.2469927

Yanlu Luo, Xueyan Zhong, Xinzhao Sun, Jiangtao Fan

{"title":"The RNA-binding protein ELAVL1 promotes Beclin1-mediated cellular autophagy and thus endometrial cancer development by affecting LncRNA-neat stability.","authors":"Yanlu Luo, Xueyan Zhong, Xinzhao Sun, Jiangtao Fan","doi":"10.1080/15384047.2025.2469927","DOIUrl":"10.1080/15384047.2025.2469927","url":null,"abstract":"Our study aims to investigate the roles of embryonic lethal abnormal vision-like 1 (ELAVL1) and long non-coding RNA (LncRNA) NEAT1 in endometrial cancer (EC), focusing on their underlying molecular mechanisms.We obtained EC cell lines (HEC-1A, Ishikawa, RL95-2, HEC-1B, and AN3CA) from ATCC. We used siRNAs (si-ELAVL1#1 and si-ELAVL1#2) and overexpression RNAs (OE ELAVL1 and OE-NEAT1) for knockdown or overexpression of ELAVL1 and LncRNA NEAT1. We also employed 3-MA (5mM) or rapamycin (100µM) to inhibit or promote autophagy. Moreover, we conducted RNA immunoprecipitation (RIP) assays to confirm the interaction between LncRNA NEAT1 and ELAVL1. Cell Counting Kit-8 (CCK-8) and transwell assays were utilized to assess cell proliferation and migration. Additionally, we measured the expression of ELAVL1 and Beclin1 through Western blotting and RT-qPCR.ELAVL1 was found to be highly expressed in EC. Furthermore, ELAVL1 promoted the proliferation, invasion, and migration of EC cells through the regulation of Beclin1-related pathways. RIP assays revealed a direct interaction between LncRNA NEAT1 and ELAVL1, with ELAVL1 stabilizing LncRNA NEAT1 mRNA in EC cells. Additionally, we observed that ELAVL1 influenced EC cell proliferation, invasion, and migration through the regulation of LncRNA NEAT1-mediated regulation of Beclin1 expression. Moreover, in an animal study, we determined that ELAVL1 influenced endometrial cancer tumor growth through its interaction with LncRNA NEAT1, which mediated Beclin1 expression in vivo.In summary, our study showed that ELAVL1 regulated the malignant behavior of endometrial cancer cells through the modulation of LncRNA NEAT1-mediated regulation of Beclin1 expression.","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2469927"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction. 修正。

IF 4.4 4区医学

Cancer Biology & Therapy Pub Date : 2025-12-01 Epub Date: 2025-04-11 DOI: 10.1080/15384047.2025.2491914

引用次数: 0

Identification of endoplasmic reticulum stress-related genes as prognostic markers in colon cancer. 鉴定作为结肠癌预后标志物的内质网应激相关基因。

IF 4.4 4区医学

Cancer Biology & Therapy Pub Date : 2025-12-01 Epub Date: 2025-04-01 DOI: 10.1080/15384047.2025.2458820

Wenjing Xu, Wei Li, Dayu Kuai, Yaqiang Li, Wei Sun, Xian Liu, Baohong Xu

{"title":"Identification of endoplasmic reticulum stress-related genes as prognostic markers in colon cancer.","authors":"Wenjing Xu, Wei Li, Dayu Kuai, Yaqiang Li, Wei Sun, Xian Liu, Baohong Xu","doi":"10.1080/15384047.2025.2458820","DOIUrl":"10.1080/15384047.2025.2458820","url":null,"abstract":"Endoplasmic reticulum stress (ERS) has been implicated in the pathogenesis of various cancers, including colon cancer, by regulating tumor cell survival, growth, and immune response. However, the specific genes involved in ERS that could serve as prognostic markers in colon cancer remain underexplored. This study aims to identify and validate endoplasmic reticulum stress related genes (ERSRGs) in colon cancer that correlate with patient prognosis, thereby enhancing the understanding of ERS in oncological outcomes and potential therapeutic targeting. We utilized bioinformatics analyses to identify ERSRGs from publicly available colon cancer datasets. Differential expression analysis and survival analysis were performed to assess the prognostic significance of these genes. Validation was conducted through quantitative real-time PCR (RT-qPCR) on selected colon cancer cell lines. Our study identified nine ERS related genes (ASNS, ATF4, ATF6B, BOK, CLU, DDIT3, MANF, SLC39A14, TRAF2) involved in critical pathways including IL-12, PI3K-AKT, IL-7, and IL-23 signaling, and linked to 1-, 3-, and 5-year survival of patients with colon cancer. A multivariate Cox model based on these ERS related genes demonstrated significant prognostic power. Further, TRAF2 strong correlated with immune cells infiltration, suggesting its potential roles in modulating immune responses in the tumor microenvironment. The RT-qPCR validation confirmed the differential expression of these genes in human colon cancer cell lines versus human normal colonic epithelial cell line. The identified ERSRGs could serve as valuable prognostic markers and may offer new insights into the therapeutic targeting of ERS in colon cancer.","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2458820"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The mitochondria as an emerging target of self-renewal in T-cell acute lymphoblastic leukemia. 线粒体作为t细胞急性淋巴细胞白血病自我更新的新靶点。

IF 4.4 4区医学

Cancer Biology & Therapy Pub Date : 2025-12-01 Epub Date: 2025-02-04 DOI: 10.1080/15384047.2025.2460252

Majd A Al-Hamaly, Evelyn Winter, Jessica S Blackburn

{"title":"The mitochondria as an emerging target of self-renewal in T-cell acute lymphoblastic leukemia.","authors":"Majd A Al-Hamaly, Evelyn Winter, Jessica S Blackburn","doi":"10.1080/15384047.2025.2460252","DOIUrl":"10.1080/15384047.2025.2460252","url":null,"abstract":"Acute lymphocytic leukemia (ALL) is the most common leukemia in children, with the T-cell subtype (T-ALL) accounting for 15% of those cases. Despite advancements in the treatment of T-ALL, patients still face a dismal prognosis following their first relapse. Relapse can be attributed to the inability of chemotherapy agents to eradicate leukemia stem cells (LSC), which possess self-renewal capabilities and are responsible for the long-term maintenance of the disease. Mitochondria have been recognized as a therapeutic vulnerability for cancer stem cells, including LSCs. Mitocans have shown promise in T-ALL both in vitro and in vivo, with some currently in early-phase clinical trials. However, due to challenges in studying LSCs in T-ALL, our understanding of how mitochondrial function influences self-renewal remains limited. This review highlights the emerging literature on targeting mitochondria in diverse T-ALL models, emphasizing specific mitochondrial vulnerabilities linked to LSC self-renewal and their potential to significantly improve T-ALL treatment.","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2460252"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11801350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The small molecule drug CBL0137 interferes with DNA damage repair and enhances the sensitivity of NK/T-Cell lymphoma to cisplatin. 小分子药物CBL0137干扰DNA损伤修复，增强NK/ t细胞淋巴瘤对顺铂的敏感性。

IF 4.4 4区医学

Cancer Biology & Therapy Pub Date : 2025-12-01 Epub Date: 2025-05-26 DOI: 10.1080/15384047.2025.2511301

Hang Gu, Siyu Qian, Yue Zhang, Mingzhi Zhang, Qingjiang Chen, Xudong Zhang

{"title":"The small molecule drug CBL0137 interferes with DNA damage repair and enhances the sensitivity of NK/T-Cell lymphoma to cisplatin.","authors":"Hang Gu, Siyu Qian, Yue Zhang, Mingzhi Zhang, Qingjiang Chen, Xudong Zhang","doi":"10.1080/15384047.2025.2511301","DOIUrl":"10.1080/15384047.2025.2511301","url":null,"abstract":"This study aimed to investigate the in vitro and in vivo antitumor effects and mechanisms of the small molecule anticancer drug CBL0137 in NK/T-cell lymphoma (NKTCL), as well as its efficacy when combined with chemotherapy or immunotherapy. Cell viability assays were performed to evaluate the inhibitory effect of CBL0137 on NKTCL cell proliferation in vitro. Flow cytometry was used to assess the effects of the drug on apoptosis and cell cycle progression. RNA sequencing (RNA-seq) was employed to explore the mechanism of action of CBL0137 in NKTCL, and Western blotting (WB) was used to validate the expression of related proteins. An in vivo xenograft model was used to confirm the antitumor activity of CBL0137. Additionally, immunohistochemistry analysis was conducted to further study tumor tissue. CBL0137 effectively inhibited the proliferation of NKTCL cells in vitro, induced apoptosis, and significantly blocked cell cycle progression. RNA-seq analysis revealed that CBL0137 exerts its antitumor effect primarily by interfering with DNA damage repair. In vivo experiments using xenografted mice confirmed the antitumor activity of CBL0137. CBL0137, when combined with PD-1 antibody, exhibits synergistic antitumor effects in mice, and its combination with cisplatin significantly enhances the sensitivity of NKTCL to cisplatin. CBL0137 inhibits DNA damage repair in NK/T-cell lymphoma and enhances its sensitivity to cisplatin.","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2511301"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12118381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dual role of CXCL10 in cancer progression: implications for immunotherapy and targeted treatment‎. CXCL10在癌症进展中的双重作用：免疫治疗和靶向治疗的意义

IF 4.6 4区医学

Cancer Biology & Therapy Pub Date : 2025-12-01 Epub Date: 2025-08-04 DOI: 10.1080/15384047.2025.2538962

Osama A Madkhali, Sivakumar S Moni, Yosif Almoshari, Fahad Y Sabei, Awaji Y Safhi

{"title":"Dual role of CXCL10 in cancer progression: implications for immunotherapy and targeted treatment‎.","authors":"Osama A Madkhali, Sivakumar S Moni, Yosif Almoshari, Fahad Y Sabei, Awaji Y Safhi","doi":"10.1080/15384047.2025.2538962","DOIUrl":"10.1080/15384047.2025.2538962","url":null,"abstract":"CXCL10 is a chemokine crucial for immune cell recruitment and inflammation modulation, especially ‎within the tumor microenvironment.‎ This review critically analyzes the underexplored role of CXCL10 in modulating ‎JAK/STAT, MAPK/ERK, and PI3K/Akt pathways across different tumor types, highlighting ‎inconsistencies in current research and proposing novel therapeutic strategies based on ‎research ‎from databases such as PubMed and Scopus. Future targeted therapies could ‎include personalized ‎approaches that either enhance the immunostimulatory functions of CXCL10‎ or inhibit its tumor promoting effects. Techniques such as CRISPR/Cas9-mediated knockout of CXCL10 has demonstrated potential in preclinical models to ‎reduce tumor-promoting inflammation, while nanoparticle-based CXCL10 inhibitors enhance ‎immune checkpoint blockade efficacy in melanoma. In addition, targeting CXCL10-related mechanisms of immune evasion such as inhibition of CXCR3 may help to prevent metastasis. Futureresearch should focus on CXCL10-targeting approaches in highly immunosuppressive tumors, such as pancreatic and glioblastoma, where immune checkpoint inhibitors have shown limited efficacy.","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2538962"},"PeriodicalIF":4.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12326575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

β-hydroxybutyrate, a ketone body, suppresses tumor growth, stemness, and invasive phenotypes in non-small cell lung cancer. β-羟基丁酸，一种酮体，抑制非小细胞肺癌的肿瘤生长、干性和侵袭性表型。

IF 4.4 4区医学

Cancer Biology & Therapy Pub Date : 2025-12-01 Epub Date: 2025-06-22 DOI: 10.1080/15384047.2025.2516825

Yunlong Huang, Jiaxuan Ding, Yufeng Zhu, Jin Shi, Rong Liu, Chunmei Wu, Liangfu Han, Mingfeng Zhang

{"title":"β-hydroxybutyrate, a ketone body, suppresses tumor growth, stemness, and invasive phenotypes in non-small cell lung cancer.","authors":"Yunlong Huang, Jiaxuan Ding, Yufeng Zhu, Jin Shi, Rong Liu, Chunmei Wu, Liangfu Han, Mingfeng Zhang","doi":"10.1080/15384047.2025.2516825","DOIUrl":"10.1080/15384047.2025.2516825","url":null,"abstract":"Lung cancer is the most common cancer worldwide. The stemness and metastasis of tumor cells present major challenges to effective lung cancer treatment. Beta-hydroxybutyrate (BHB), a ketone body, plays a key role in various cancers. However, whether BHB mediates the progression of non-small cell lung cancer (NSCLC) remains unclear. The effects of BHB on the proliferation, apoptosis, and metastasis of NSCLC cells were assessed using the Cell Counting Kit 8, flow cytometry, western blotting, and Transwell assays. The sphere formation assay was used to evaluate the impact of BHB on NSCLC cell stemness. The underlying molecular mechanism was investigated through knockdown and overexpression of free fatty acid receptor 3 (FFAR3) using shRNAs and expression vectors in two NSCLC cell lines (NCI-H1975 and PC-9). In vivo, xenograft tumor and liver metastasis models were established in nude mice. BHB treatment reduced viability, stemness, and migratory and invasive abilities of NSCLC cells. BHB also induced apoptosis and increased cleaved caspase-3 levels in these cells. Moreover, BHB suppressed tumor growth and metastasis, and reduced cell stemness in NSCLC tissues in vivo. Mechanistically, FFAR3 knockdown abolished, while FFAR3 overexpression enhanced, the tumor-suppressive effects of BHB, identifying FFAR3 as a key mediator. These data shed light on the role of BHB in NSCLC development and its underlying molecular mechanisms, suggesting a promising treatment strategy for patients with NSCLC.","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2516825"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367930","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}

引用次数: 0

USP44 promotes chemotherapeutic drug resistance of triple negative breast cancer through EZH2 protein stability. USP44通过EZH2蛋白稳定性促进三阴性乳腺癌化疗耐药

IF 4.4 4区医学

Cancer Biology & Therapy Pub Date : 2025-12-01 Epub Date: 2025-07-06 DOI: 10.1080/15384047.2025.2529652

Pu Wu, Wanting Xiao, Junjie Ni, Yuming Lou, Chaoyang Xu

{"title":"USP44 promotes chemotherapeutic drug resistance of triple negative breast cancer through EZH2 protein stability.","authors":"Pu Wu, Wanting Xiao, Junjie Ni, Yuming Lou, Chaoyang Xu","doi":"10.1080/15384047.2025.2529652","DOIUrl":"10.1080/15384047.2025.2529652","url":null,"abstract":"Triple negative breast cancer (TNBC), a highly invasive breast cancer, is one of the leading causes of cancer-related mortality worldwide. Although chemotherapy remains the standard of care for TNBC, the development of chemotherapy resistance significantly limits its clinical efficacy. In this study, we identified the deubiquitinating enzyme USP44 as a contributor to chemoresistance in TNBC and investigated the potential regulatory feedback mechanisms involved. In this experimental study, we investigated the sensitivity of TNBC cells MDA-MB-231 and BT-549 to chemotherapy drugs after overexpression and knockdown of USP44 using CCK-8 reagent kit and flow cytometry analysis, respectively. Western blot was performed to evaluate the expression levels of relevant proteins. In vivo xenograft models were established to examine the effects of USP44 and its downstream targets on chemosensitivity. Co-immunoprecipitation assay and ubiquitination assay were conducted to identify interacting proteins and elucidate the underlying molecular mechanisms. Knockdown of USP44 increased the sensitivity of MDA-MB-231 and BT-549 cells to chemotherapeutic agents, accompanied by elevated levels of Cleaved PARP. In contrast, USP44 overexpression reduced drug sensitivity. Mechanistically, USP44 was found to interact with EZH2, preventing its ubiquitination and subsequent proteasomal degradation. Notably, treatment with GSK126, a specific EZH2 inhibitor, reversed the chemoresistance induced by USP44 overexpression. USP44/EZH2 signaling pathway is one of the key to causing the drug resistance of TNBC, warranting further clinical investigation.","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2529652"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12233816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0