Cancer Biology & Therapy最新文献

{"title":"<i>PCK2</i> promotes invasion and epithelial-to-mesenchymal transition in triple-negative breast cancer by promoting TGF-β/SMAD3 signaling through inhibiting TRIM67-mediated SMAD3 ubiquitination.","authors":"Tsung-Ming Chang, Wei-Yu Fang, Hui-Ping Hsu, Pei-Yi Chu, Shih Sheng Jiang, Kuo-Wei Huang, Wen-Chun Hung, Hui-You Lin, Hui-Jen Tsai","doi":"10.1080/15384047.2025.2478670","DOIUrl":"10.1080/15384047.2025.2478670","url":null,"abstract":"<p><p><i>PCK2</i>, which encodes mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M), is upregulated in various cancers. We demonstrated high expression of PEPCK-M in approximately half of triple-negative breast cancers (TNBCs) previously. TNBC is associated with an aggressive phenotype and a high metastasis rate. In this study, we investigated the role of <i>PCK2</i> in TNBC. <i>PCK2</i> knockdown suppressed proliferation and mTOR signaling in TNBC cells. In addition, cell invasion/migration ability and the expression of epithelial-to-mesenchymal transition (EMT) markers were positively correlated with <i>PCK2</i> expression in TNBC cells via regulation of transforming growth factor-β (TGF-β)/SMAD3 signaling. <i>SMAD3</i> was positively regulated by <i>PCK2</i> in TNBC cells. Knockdown of <i>SMAD3</i> in <i>PCK2</i>-overexpressing TNBC cells reduced the expression levels of EMT markers, Snail and Slug, and suppressed cell invasion/migration. In addition, <i>PCK2</i> knockdown attenuated the stimulatory effect of TGF-β on SMAD3 phosphorylation in TNBC cells. PEPCK-M promotes the protein and mRNA expression of SMAD3 via competitive binding to tripartite motif-containing 67 (TRIM67), an E3 ubiquitin ligase, to reduce SMAD3 ubiquitination, which leads to promoting nuclear translocation of SMAD3 and autoregulation of SMAD3 transcription. Moreover, high <i>PCK2</i> mRNA expression was significantly associated with poor survival in TNBC patients. In conclusion, our study revealed for the first time that <i>PCK2</i> activates TGF-β/SMAD3 signaling by regulating the expression and phosphorylation of SMAD3 by inhibiting TRIM67-mediated SMAD3 ubiquitination and promoting the stimulatory effect of TGF-β to promote TNBC invasion. The regulatory effect of <i>PCK2</i> on mTOR and TGF-β/SMAD3 signaling suggests that <i>PCK2</i> is a potential therapeutic target for suppressing TNBC progression.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2478670"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623809","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}

{"title":"Targeting the IKZF1/BCL-2 axis as a novel therapeutic strategy for treating acute T-cell lymphoblastic leukemia.","authors":"Juan Li, Chunmei Ye, Hui Li, Jun Li","doi":"10.1080/15384047.2025.2457777","DOIUrl":"10.1080/15384047.2025.2457777","url":null,"abstract":"<p><strong>Objectives: </strong>Acute T-cell lymphoblastic leukemia (T-ALL) is a severe hematologic malignancy with limited treatment options and poor long-term survival. This study explores the role of IKZF1 in regulating BCL-2 expression in T-ALL.</p><p><strong>Methods: </strong>CUT&Tag and CUT&Run assays were employed to assess IKZF1 binding to the BCL-2 promoter. IKZF1 overexpression and knockdown experiments were performed in T-ALL cell lines. The effects of CX-4945 and venetoclax, alone and in combination, were evaluated in vitro and in vivo T-ALL models.</p><p><strong>Results: </strong>CUT&Tag sequencing identified IKZF1 binding to the BCL-2 promoter, establishing it as a transcriptional repressor. Functional assays demonstrated that IKZF1 overexpression reduced BCL-2 mRNA levels and increased repressive histone marks at the BCL-2 promoter, while IKZF1 knockdown led to elevated BCL-2 expression. CX-4945, a CK2 inhibitor, could reduced BCL-2 levels in T-ALL cells. Notably, knockdown of IKZF1 partially rescued the CX-4945-induced repression of BCL-2. These results underscore the CK2-IKZF1 signaling axis as a key regulator of BCL-2 expression. In vitro, CX-4945 enhanced the cytotoxicity of venetoclax, with the combination showing significant synergistic effects and increased apoptosis in T-ALL cell lines. In vivo studies with cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models demonstrated that CX-4945 and venetoclax combined therapy provided superior therapeutic efficacy, reducing tumor burden and prolonging survival compared to single-agent treatments.</p><p><strong>Conclusions: </strong>IKZF1 represses BCL-2 in T-ALL, and targeting the CK2-IKZF1 axis with CX-4945 and venetoclax offers a promising therapeutic strategy, showing enhanced efficacy and potential as a novel treatment approach for T-ALL.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2457777"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11776473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058197","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}

{"title":"RSK4 promotes the metastasis of clear cell renal cell carcinoma by activating RUNX1-mediated angiogenesis.","authors":"Jing Ma, Yanru Yang, Kaijing Wang, Jin Liu, Junyi Feng, Gongcheng Wang, Shuangping Guo, Linni Fan","doi":"10.1080/15384047.2025.2452025","DOIUrl":"10.1080/15384047.2025.2452025","url":null,"abstract":"<p><p>Ribosomal S6 protein kinase 4 (RSK4), a member of the serine‒threonine kinase family, plays a vital role in the Ras‒MAPK pathway. This kinase is responsible for managing several cellular activities, including cell growth, proliferation, survival, and mobility. In this study, we observed higher RSK4 protein expression in clear cell renal cell carcinoma (ccRCC) than in normal kidney tissue, and the overexpression of RSK4 might predict poor outcomes for ccRCC patients. Notably, renal cell carcinoma (RCC) is rich in blood vessels; therefore, this study aimed to explore the biological function of RSK4 in ccRCC progression and its specific regulatory mechanism. We analyzed changes in the expression of target genes through transcriptomic and proteomic assessments. We also conducted tube formation assays and VEGF ELISAs to understand the role of RSK4 in angiogenesis. Additionally, we evaluated the regulatory effect of RUNX1 on EPHA2 transcription using a luciferase reporter gene assay and observed that the effect of RUNX1 on activating EPHA2 transcription was negated after the binding site was mutated. Our findings suggested that RSK4 enhanced tube formation by stimulating VEGF secretion. Concurrently, in vivo experiments confirmed that RSK4 expedited RCC metastasis and angiogenesis. This evidence indicates that RSK4 may serve as a new prognostic marker and play a vital role in RCC metastasis.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2452025"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142963826","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}

{"title":"Upregulation of TTYH3 by lncRNA LUCAT1 through interacting with ALYREF facilitates the metastasis in non-small cell lung cancer.","authors":"Fang Fang, Mei Zhao, Jinming Meng, Jiaqi He, Chunlei Yang, Changhong Wang, Jiaxiao Wang, Sheng Xie, Xiaowei Jin, Wei Shi","doi":"10.1080/15384047.2025.2464966","DOIUrl":"10.1080/15384047.2025.2464966","url":null,"abstract":"<p><p>Metastasis is the predominant culprit of cancer-associated mortality in non-small cell lung cancer (NSCLC). Tweety homolog 3 (TTYH3) reportedly functions vitally in the development of diverse cancers, including NSCLC; nevertheless, its role in NSCLC metastasis remains ambiguous. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot were initially employed to detect TTYH3 expression in NSCLC and normal lung epithelial cells. Subsequently, A549 and NCI-H1650 cells were chosen as NSCLC models in vitro and transfected with short hairpin RNAs (sh-TTYH3, sh-LUCAT1, and sh-ALYREF) or overexpression plasmids (oe-ALYREF and oe-TTYH3). Transwell assays were used for migrative and invasive tests. Epithelial mesenchymal transformation (EMT)-related proteins (E-cadherin, N-cadherin, Vimentin, and Snail) were measured by western blot. A mouse lung metastasis model was built to define the function of TTYH3 in NSCLC metastasis, followed by hematoxylin-eosin staining. RNA pull-down, RNA immunoprecipitation, qRT-PCR, western blot, and actinomycin D assays were adopted to determine the relationships among LUCAT1, ALYREF, and TTYH3. TTYH3 was highly expressed in NSCLC cells relative to normal lung cells. Functionally, TTYH3 knockdown restrained NSCLC migration, invasion, EMT, and metastasis. Mechanistic experiments demonstrated that LUCAT1 bound to ALYREF. After LUCAT1 knockdown, TTYH3 expression and mRNA stability were reduced, which was reversed by ALYREF overexpression. Furthermore, ALYREF overexpression counteracted the inhibitory effects of LUCAT1 knockdown on NSCLC cell migration, invasion, and EMT. TTYH3 overexpression eliminated the suppressive functions of ALYREF downregulation in NSCLC progression. LUCAT1 promotes TTYH3 expression via interacting with ALYREF, thereby facilitating NSCLC migration, invasion, and EMT.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2464966"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11817527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390185","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}

{"title":"First-line treatments for KRAS-mutant non-small cell lung cancer: current state and future perspectives.","authors":"Qi He, Xiaoyan Liu, Liyan Jiang, Ping Liu, Weixia Xuan, Yudong Wang, Rui Meng, Huijing Feng, Shuang Lv, Qian Miao, Di Zheng, Yan Xu, Mengzhao Wang","doi":"10.1080/15384047.2024.2441499","DOIUrl":"10.1080/15384047.2024.2441499","url":null,"abstract":"<p><p><i>KRAS</i> mutations are common in non-small cell lung cancer (NSCLC) and are associated with patient prognosis; however, targeting <i>KRAS</i> has faced various difficulties. Currently, immunotherapy, chemotherapy, and chemoimmunotherapy play pivotal roles in the first-line treatment of <i>KRAS</i>-mutated NSCLC. Here, we summarize the current evidence on first-line therapies and compare the treatment outcomes and biomarkers for different regimens. KRAS inhibitors and other emerging alternative treatments are also discussed, as combining these drugs with immunotherapy may serve as a promising first-line treatment for <i>KRAS</i>-mutated NSCLC in the future. We hope that this review will assist in first-line treatment choices and shed light on the development of novel agents for <i>KRAS</i>-mutated NSCLC.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2441499"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833913","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}

{"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":"<p><strong>Background: </strong>While NDUFAF6 is implicated in breast cancer, its specific role remains unclear.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>Knockdown of NDUFAF6 resulted in apoptosis and mitophagy in breast cancer cells and NDUFAF6 may be a potential molecular target for breast cancer therapy.</p>","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}

{"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":"<p><p>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.</p>","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}

{"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":"<p><p>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.</p>","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}

{"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":"<p><p>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 <i>in vitro</i> and <i>in vivo</i>, 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.</p>","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}

{"title":"Caspase 3-specific cleavage of ubiquitin-specific peptidase 48 enhances drug-induced apoptosis in AML.","authors":"Zhanglin Zhang, Xiang Lin, Yaling Yang, Xuemei Wang, Yi Wang, Xianbao Huang, Miao Hong, Wei Gao, Hua He, M James You, Yi Yang, Guangyao Kong","doi":"10.1080/15384047.2025.2459426","DOIUrl":"10.1080/15384047.2025.2459426","url":null,"abstract":"<p><p>Dysfunction or dysregulation of deubiquitination is closely related to the initiation and development of multiple cancers. Targeted regulation of deubiquitination has been recognized as an important strategy in tumor therapy. However, the mechanism by which drugs regulate deubiquitinase is not clear. Here, we identified ubiquitin-specific peptidase 48 (USP48), a member of the ubiquitin-specific protease family highly expressed in various tumors, as a specific substrate for the activated caspase-3. During drug induced apoptosis of AML cells, activated caspase-3 cleaves USP48 through recognizing the conservative motif DEQD located at 611-614 sites of human USP48. Subsequent analysis showed that the cleavage USP48 N-terminal fragment which contains catalytic active domain is easily degraded by ubiquitination. Meanwhile knockdown experiment showed that inhibiting the expression of USP48 could also promotes apoptosis and enhance the efficacy of chemotherapy drugs. Altogether, these results suggest that targeting USP48 may represent a novel therapeutic strategy in AML.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2459426"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058280","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}