IF 9.1 1区医学

Oncogene Pub Date : 2026-09-04 DOI: 10.1038/s41388-026-03964-w

Marija A Zarocsinceva, Moosa Qureshi, Nicola K Wilson, George Giotopoulos, Blaise Musabe, Katherine H M Sturgess, M S Vijayabaskar, Sarah J Kinston, Ryan Asby, David J Adams, Brian J P Huntly, Fernando J Calero-Nieto, Berthold Göttgens

{"title":"A step-wise, deterministic and fatal mouse model of myeloid neoplasm with spontaneous acquisition of patient-relevant RTK-RAS mutations.","authors":"Marija A Zarocsinceva, Moosa Qureshi, Nicola K Wilson, George Giotopoulos, Blaise Musabe, Katherine H M Sturgess, M S Vijayabaskar, Sarah J Kinston, Ryan Asby, David J Adams, Brian J P Huntly, Fernando J Calero-Nieto, Berthold Göttgens","doi":"10.1038/s41388-026-03964-w","DOIUrl":"https://doi.org/10.1038/s41388-026-03964-w","url":null,"abstract":"Leukaemia arises through the stepwise transformation of healthy haematopoietic cells, yet the asymptomatic premalignant phase and its progression to overt disease remain poorly understood. To model this process, we engineered a patient-derived CEBPA mutation into Hoxb8-FL multipotent murine progenitors and transplanted them into syngeneic mice, capturing a clinically silent premalignant stage. All recipients developed overt disease after ~12 months with 100% penetrance and all acquired secondary RTK-RAS mutations, often with identical amino acid changes to those in patients. Single-cell transcriptomics and phenotypic profiling showed that premalignant mutant cells adopt a plasmacytoid dendritic progenitor-like state in vitro which generates both myeloid and B-lymphoid lineages during premalignancy in vivo, with individual tumours restricted to one lineage. The specificity for RTK-RAS mutations coupled with ongoing differentiation, reflects clinically relevant biological contexts thus providing a tractable model of myeloid neoplasm for mechanistic studies and drug discovery.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148892210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

ITGA5 promotes homologous recombination mediated radioresistance in esophageal squamous cell carcinoma by upregulating RAD51AP1 expression. ITGA5通过上调RAD51AP1表达促进同源重组介导的食管鳞状细胞癌放射耐药。

IF 9.1 1区医学

Oncogene Pub Date : 2026-09-04 DOI: 10.1038/s41388-026-03966-8

Xinyi Huang, Jiayi Liu, Jiao Ren, Jupeng Yuan, Wen Huo, Zengfu Zhang, Minxin Chen, Baoqing Tian, Dawei Chen

{"title":"ITGA5 promotes homologous recombination mediated radioresistance in esophageal squamous cell carcinoma by upregulating RAD51AP1 expression.","authors":"Xinyi Huang, Jiayi Liu, Jiao Ren, Jupeng Yuan, Wen Huo, Zengfu Zhang, Minxin Chen, Baoqing Tian, Dawei Chen","doi":"10.1038/s41388-026-03966-8","DOIUrl":"https://doi.org/10.1038/s41388-026-03966-8","url":null,"abstract":"Radiotherapy resistance represents a critical barrier to successful treatment of esophageal squamous cell carcinoma (ESCC), driving tumor recurrence and poor patient survival. We identify constitutive overexpression of integrin α5 (ITGA5) as a key molecular determinant of ESCC radioresistance. Clinically, elevated ITGA5 expression correlates with radiation therapy failure and reduced overall survival. Mechanistically, ITGA5 sustains persistent FAK/AKT/GSK-3β/β-Catenin signaling activation, which drives MYC-dependent transactivation of RAD51AP1. This signaling axis enhances homologous recombination repair efficiency by facilitating RAD51 chromatin loading, enabling effective DNA damage resolution and radioresistance maintenance. Genetic validation confirms the indispensable roles of RAD51AP1 and MYC in this process. Critically, pharmacological inhibition of ITGA5 with ATN-161 restores radiation sensitivity in preclinical models, suppressing tumor growth and enhancing DNA damage accumulation. Our work defines the ITGA5/FAK/β-catenin/MYC/RAD51AP1 pathway as a key mechanistic driver of radioresistance and validates ITGA5 as a potential clinical target for ESCC therapy.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148892145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 La/SSB is associated with HNSCC progression and TFAP2C/FSCN1-linked transcriptional regulation. rna结合蛋白La/SSB与HNSCC进展和TFAP2C/ fscn1相关的转录调控有关。

IF 9.1 1区医学

Oncogene Pub Date : 2026-09-03 DOI: 10.1038/s41388-026-03959-7

Shixian Liu, Deshang Chen, Wentao Zhang, Hui Li, Jie Peng, Xiaomin Wang, Mingjie Zhang, Weiwei Liu, Junjie Zhang, Mengjun Wang, Guoying Han, Changqi Cai, Shencheng Liu, Xiaoli You, Qun Xu, Yuefeng Han, Xiaojun Zha, Shiyin Ma

{"title":"The RNA-binding protein La/SSB is associated with HNSCC progression and TFAP2C/FSCN1-linked transcriptional regulation.","authors":"Shixian Liu, Deshang Chen, Wentao Zhang, Hui Li, Jie Peng, Xiaomin Wang, Mingjie Zhang, Weiwei Liu, Junjie Zhang, Mengjun Wang, Guoying Han, Changqi Cai, Shencheng Liu, Xiaoli You, Qun Xu, Yuefeng Han, Xiaojun Zha, Shiyin Ma","doi":"10.1038/s41388-026-03959-7","DOIUrl":"https://doi.org/10.1038/s41388-026-03959-7","url":null,"abstract":"Head and neck squamous cell carcinoma (HNSCC) is characterized by aggressive progression, frequent therapeutic resistance, and poor clinical outcomes. Although the RNA-binding protein La/SSB is aberrantly expressed in multiple malignancies, its functional and mechanistic role in HNSCC remains incompletely understood. Here, by integrating transcriptomic and chromatin accessibility profiling with comprehensive in vitro and in vivo analyses, we identify La/SSB as a putative regulator associated with HNSCC progression and cisplatin (CDDP) resistance. La/SSB was markedly upregulated in HNSCC tissues and cell lines, and elevated expression was associated with unfavorable survival. Genetic depletion of La/SSB suppressed proliferation, migration, and invasion, promoted apoptosis, and reduced tumor growth and metastatic colonization, whereas ectopic expression exerted the opposite effects. Multi-omics analyses implicated FSCN1 as a functionally relevant downstream candidate associated with La/SSB-dependent phenotypes. Mechanistically, La/SSB depletion was associated with reduced H3K27ac enrichment and diminished TFAP2C occupancy at the FSCN1 promoter, supporting a TFAP2C/FSCN1-linked regulatory framework. Importantly, loss of La/SSB significantly enhanced CDDP responsiveness in the PDO model established in this study and in vivo conditional knockout models. Clinically, elevated La/SSB showed independent prognostic value, whereas TFAP2C and FSCN1 supported a biologically associated regulatory framework linked to aggressive disease features. Collectively, our findings identify La/SSB as a clinically relevant factor associated with HNSCC progression and CDDP responsiveness, and support a TFAP2C/FSCN1-linked regulatory framework that may contribute to malignant phenotypes.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148888234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 GSEC-encoded polypeptide GESP drives colorectal cancer tumorigenesis via NPM1-c-Myc-mediated repression of NDRG1. gsec编码的多肽GESP通过npm1 -c- myc介导的NDRG1抑制驱动结直肠癌的肿瘤发生。

IF 9.1 1区医学

Oncogene Pub Date : 2026-09-01 DOI: 10.1038/s41388-026-03958-8

Yoshihiro Kawasaki, Tomoatsu Hayashi, Akane Kitta-Kunihiro, Lumi Negishi, Sakiko Suda, Chiemi Furuya-Ikude, Nao Taniguchi, Tetsu Akiyama, Eisaku Kondo

{"title":"The GSEC-encoded polypeptide GESP drives colorectal cancer tumorigenesis via NPM1-c-Myc-mediated repression of NDRG1.","authors":"Yoshihiro Kawasaki, Tomoatsu Hayashi, Akane Kitta-Kunihiro, Lumi Negishi, Sakiko Suda, Chiemi Furuya-Ikude, Nao Taniguchi, Tetsu Akiyama, Eisaku Kondo","doi":"10.1038/s41388-026-03958-8","DOIUrl":"https://doi.org/10.1038/s41388-026-03958-8","url":null,"abstract":"Expression of long non-coding RNAs (lncRNAs) is frequently dysregulated in human cancers. We previously reported that the lncRNA GSEC accelerates colorectal cancer (CRC) cell motility by inhibiting the RNA helicase DHX36. Here, we demonstrated that a nuclear polypeptide (designated 'GESP') is translated from a short ORF encoded by GSEC, which is highly expressed in CRC cells. In vivo experiments using CRC cell-xenografted mice revealed that GESP is required for development of immature tumors through suppression of a critical differentiation factor, NDRG1. Suppression of GESP by shRNA-mediated knockdown of GSEC caused growth retardation associated with tumor differentiation. At the molecular level, GESP recruits c-Myc to the promoter region of NDRG1 by forming a GESP-NPM1-c-Myc complex, which consequently represses transcription of NDRG1. Collectively, these data indicate a novel lncRNA product, GESP, plays a pivotal role in CRC tumor development/progression by suppression of tumor cell differentiation through the GESP-NDRG1 axis.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Neuromedin U 'innervation' reprograms myeloid immunosuppression in neuroendocrine prostate cancer. Neuromedin U“神经支配”在神经内分泌前列腺癌中重编程髓系免疫抑制。

IF 9.1 1区医学

Oncogene Pub Date : 2026-09-01 DOI: 10.1038/s41388-026-03969-5

Michela Perego, Jozef Madzo, Andrew V Kossenkov, F Cansu Atilgan, Marcella Tazzari, Maria Maddalena Tumedei, Francesco Limarzi, Cristian Lolli, Giorgia Gurioli, Alessandro Fatatis, Mary V Iacocca, Nicholas J Petrelli, Justine J Jacobi, David W Goodrich, Lucia R Languino, Dario C Altieri

{"title":"Neuromedin U 'innervation' reprograms myeloid immunosuppression in neuroendocrine prostate cancer.","authors":"Michela Perego, Jozef Madzo, Andrew V Kossenkov, F Cansu Atilgan, Marcella Tazzari, Maria Maddalena Tumedei, Francesco Limarzi, Cristian Lolli, Giorgia Gurioli, Alessandro Fatatis, Mary V Iacocca, Nicholas J Petrelli, Justine J Jacobi, David W Goodrich, Lucia R Languino, Dario C Altieri","doi":"10.1038/s41388-026-03969-5","DOIUrl":"https://doi.org/10.1038/s41388-026-03969-5","url":null,"abstract":"Neuroendocrine prostate cancer (NEPC) is an increasingly recognized, highly aggressive disease variant with no actionable therapeutic targets and a life expectancy of 7 months or less. Using a transgenic mouse model, we now show that early stages of NEPC are associated with increased intraprostatic recruitment of Ly6G+ polymorphonuclear neutrophils (PMN) and reduced infiltration of CD8+ T cells. This coincided with expansive transcriptional changes of increased cell viability and cell migration, as well as upregulation of multiple neuronal mediators with the neuropeptide, Neuromedin U (NMU) as the top hit (Z score = 4.34; FDR < 5%; p = 3.62 × 10-9). Analysis of a large cohort of human patient samples revealed that NMU was highly expressed in early and late stage prostate cancer, preferentially segregating with AR-/NE+ metastases. Exposure of PMN to recombinant NMU was sufficient to stimulate cell migration, inflammatory gene expression with increased levels of the cytokine-like alarmin, S100A9 and suppression of T cell proliferation. Genetic or pharmacological targeting of NMU/S100A9 signaling inhibited NEPC growth, reinvigorated an intratumoral immune microenvironment via recruitment of tumor antigen-specific CD8+ T cells with 'stem-like' (TCF1+/PD1+) and cytotoxic (GrzB+/KLRG1+) properties and enhanced the activity of therapeutic immune checkpoint inhibition, in vivo. Therefore, NMU 'innervation' drives myeloid immunosuppression in NEPC and provides a therapeutic target to restore sensitivity to immunotherapy in this highly refractory malignancy.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Frequently amplified SHANK2 promotes esophageal squamous cell carcinoma progression through the DVL/YAP axis. 频繁扩增的SHANK2通过DVL/YAP轴促进食管鳞状细胞癌的进展。

IF 9.1 1区医学

Oncogene Pub Date : 2026-08-31 DOI: 10.1038/s41388-026-03974-8

Cuicui Wang, Wei Zhao, Man Li, Min He, Cuicui Xu, Jianming Hu, Jun Hou, Lianghai Wang

{"title":"Frequently amplified SHANK2 promotes esophageal squamous cell carcinoma progression through the DVL/YAP axis.","authors":"Cuicui Wang, Wei Zhao, Man Li, Min He, Cuicui Xu, Jianming Hu, Jun Hou, Lianghai Wang","doi":"10.1038/s41388-026-03974-8","DOIUrl":"https://doi.org/10.1038/s41388-026-03974-8","url":null,"abstract":"SHANK2 is crucial for neuronal synapse development and has been implicated in certain tumors; however, its role in esophageal squamous cell carcinoma (ESCC) remains underexplored. In this study, the expression and prognostic significance of SHANK2 in ESCC were assessed through bioinformatics analyses and immunohistochemical staining. We examined the relationship between SHANK2 expression and genetic alterations across multiple ESCC datasets. The effects of SHANK2 on cell proliferation, migration, and invasion were evaluated using cell-based assays. Potential SHANK2-interacting proteins were identified via co-immunoprecipitation followed by mass spectrometry and further validated using immunoprecipitation and immunoblotting. Additionally, we investigated the in vivo role of SHANK2 in ESCC progression using tumor xenograft mouse models. Our findings demonstrated that SHANK2 expression was significantly elevated in ESCC tissues, with high levels correlating with poor patient prognosis. Genetic amplification of SHANK2 was frequently observed in ESCC samples. SHANK2 promoted the proliferation, motility, and epithelial-mesenchymal transition of ESCC cells. Mechanistically, SHANK2 may activate the YAP signaling through competitive binding with DVL2, thereby facilitating malignant progression. In vivo studies indicated that targeting YAP signaling can mitigate SHANK2-induced ESCC growth. Taken together, SHANK2 is upregulated in ESCC and activates YAP signaling by interacting with DVL2, contributing to tumor progression. The SHANK2/DVL/YAP axis presents a potential therapeutic target for ESCC.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

POC1A promotes the proliferation, metastasis and stemness of bladder cancer by stabilizing BMI1 via USP7. POC1A通过USP7稳定BMI1，促进膀胱癌的增殖、转移和干性。

IF 9.1 1区医学

Oncogene Pub Date : 2026-08-31 DOI: 10.1038/s41388-026-03973-9

Houyi Wei, Renran Bai, Jianmin Liu, Lei Lyu, Jingdong Yuan, Wan Xiang, Kaiyu Qian, Fangjin Chen, Lingao Ju, Yi Zhang, Yu Xiao, Gang Wang

{"title":"POC1A promotes the proliferation, metastasis and stemness of bladder cancer by stabilizing BMI1 via USP7.","authors":"Houyi Wei, Renran Bai, Jianmin Liu, Lei Lyu, Jingdong Yuan, Wan Xiang, Kaiyu Qian, Fangjin Chen, Lingao Ju, Yi Zhang, Yu Xiao, Gang Wang","doi":"10.1038/s41388-026-03973-9","DOIUrl":"https://doi.org/10.1038/s41388-026-03973-9","url":null,"abstract":"Advanced bladder cancer (BLCA), a malignancy with high recurrence, carries a dismal prognosis, demanding the identification of novel therapeutic targets. In this study, we aim to investigate a critical molecular mechanism driving BLCA progression. By integrating published sequencing datasets, we identified that POC1A is overexpressed in BLCA tissues, a factor positively correlated with advanced stage, high grade, disease progression, and inversely correlated with overall survival. In vitro and in vivo analyses indicate that POC1A knockdown inhibits BLCA cell proliferation, metastasis, and stemness. Mechanistically, POC1A functions as a scaffold protein, forming a complex with USP7 and BMI1. This enhances the USP7-BMI1 interaction, reduces BMI1 ubiquitination in a USP7-dependent manner, and consequently stabilizes the BMI1 protein. The functional significance of this pathway was confirmed as overexpression of either BMI1 or USP7 rescued the inhibitory phenotypes induced by POC1A knockdown. Furthermore, pharmacological targeting of BMI1 with Unesbulin suppressed BLCA growth in cell-line and patient-derived xenograft models, supporting the therapeutic tractability of the POC1A-BMI1 axis. Taken together, these findings reveal that POC1A facilitates the USP7-mediated deubiquitination and stabilization of BMI1, establishing the POC1A-USP7-BMI1 complex as a compelling therapeutic target in BLCA.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

DHCR24⁺ tumor epithelial cells drive cisplatin resistance in bladder cancer by enhancing cholesterol metabolism to activate lipid raft-associated MAPK signaling. DHCR24+肿瘤上皮细胞通过增强胆固醇代谢激活脂质筏相关的MAPK信号，驱动膀胱癌顺铂耐药。

IF 9.1 1区医学

Oncogene Pub Date : 2026-08-29 DOI: 10.1038/s41388-026-03967-7

Yuanqiao Zhao, Zhuo Xing, Mengmeng Wang, Liangmin Fu, Ruilin Liu, Zexian Ding, Yuan Li, Yinhuai Wang, Bin Yan, Xueqiang Zhu

{"title":"DHCR24+ tumor epithelial cells drive cisplatin resistance in bladder cancer by enhancing cholesterol metabolism to activate lipid raft-associated MAPK signaling.","authors":"Yuanqiao Zhao, Zhuo Xing, Mengmeng Wang, Liangmin Fu, Ruilin Liu, Zexian Ding, Yuan Li, Yinhuai Wang, Bin Yan, Xueqiang Zhu","doi":"10.1038/s41388-026-03967-7","DOIUrl":"https://doi.org/10.1038/s41388-026-03967-7","url":null,"abstract":"Cisplatin-based combination therapy remains the primary treatment modality for patients with advanced bladder cancer (BCa); however, the emergence of drug resistance severely restricts clinical benefits. The molecular mechanisms underlying chemoresistance remain incompletely understood. By integrating single-cell transcriptomics with in vitro and in vivo experiments, we revealed that cholesterol metabolism was significantly hyperactivated in cisplatin-resistant BCa tissues. Further subpopulation re-clustering identified a specific chemoresistant epithelial cell subset (C3) characterized by robust cholesterol metabolism, in which the cholesterol metabolic enzyme DHCR24 was significantly upregulated and played a pivotal role in mediating cisplatin resistance in BCa. Mechanistically, the elevated expression of TFDP1 in cisplatin-resistant BCa epithelial cells upregulated DHCR24 via the formation of the TFDP1-E2F1 transcriptional complex, thereby promoting cholesterol biosynthesis. The enriched intracellular cholesterol facilitated the formation of cell membrane lipid rafts and enhanced the phosphorylation of Src, which in turn hyperactivated the downstream MAPK signaling pathway, ultimately conferring cisplatin resistance. Furthermore, the accumulated cholesterol enhanced PD-L1 protein stability, thereby impairing the efficacy of immunotherapy in BCa. Taken together, our study characterizes a specific DHCR24+ tumor epithelial subpopulation that orchestrates cisplatin resistance via the \"cholesterol-lipid raft-MAPK\" axis. These findings establish a clear mechanistic link between cholesterol metabolism and cisplatin sensitivity.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148857551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Correction: E-cadherin is a biomarker for ferroptosis sensitivity in diffuse gastric cancer 更正：e -钙粘蛋白是弥漫性胃癌中铁下垂敏感性的生物标志物。

IF 9.1 1区医学

Oncogene Pub Date : 2026-08-27 DOI: 10.1038/s41388-026-03963-x

Alexander M. Minikes, Yu Song, Yan Feng, Changhwan Yoon, Sam S. Yoon, Xuejun Jiang

引用次数: 0

SEC14L2 contributes to tumor progression by enhancing USP5-driven RBM3 deubiquitination in pancreatic ductal adenocarcinoma. 在胰腺导管腺癌中，SEC14L2通过增强usp5驱动的RBM3去泛素化来促进肿瘤进展。

IF 9.1 1区医学

Oncogene Pub Date : 2026-08-26 DOI: 10.1038/s41388-026-03968-6

Zengyu Feng, Kai Qin, Haocheng Yu, Chuanshuai Lin, Yuheng Tu, Jianyao Lou, Kexian Li, Juyong Liang, Hongxia Xu, Chenghong Peng

{"title":"SEC14L2 contributes to tumor progression by enhancing USP5-driven RBM3 deubiquitination in pancreatic ductal adenocarcinoma.","authors":"Zengyu Feng, Kai Qin, Haocheng Yu, Chuanshuai Lin, Yuheng Tu, Jianyao Lou, Kexian Li, Juyong Liang, Hongxia Xu, Chenghong Peng","doi":"10.1038/s41388-026-03968-6","DOIUrl":"https://doi.org/10.1038/s41388-026-03968-6","url":null,"abstract":"Pancreatic ductal adenocarcinoma (PDAC) persists as a highly lethal malignancy with a dire prognosis and scarce therapeutic advancements, highlighting an urgent demand for innovative prognostic markers and molecular targets. Herein, we identify Section 14-like lipid binding 2 (SEC14L2) as a pivotal oncogene in PDAC pathogenesis. Elevated SEC14L2 expression is established as a potent and consistent prognostic indicator, strongly associated with adverse clinical outcomes across multiple independent patient cohorts. Functional analyses confirm that SEC14L2 drives malignant progression by enhancing proliferation and inhibiting apoptosis in PDAC cells. Mechanistically, we elucidate that SEC14L2 orchestrates the recruitment of ubiquitin-specific-processing protease 5 (USP5) to RNA-binding motif protein 3 (RBM3). This interaction facilitates USP5-mediated deubiquitination of RBM3 at lysine 84, specifically cleaving K48-linked polyubiquitin chains, which consequently stabilizes the RBM3 protein. The accumulated RBM3 then augments the mRNA stability of doublecortin-like kinase 1 (DCLK1), a recognized mediator of tumorigenesis. Furthermore, we uncover that the transcription factor SP1 acts as a key upstream regulator, directly governing the transcriptional activation of SEC14L2 and fostering its frequent upregulation in PDAC. Our findings delineate a novel SP1/SEC14L2/USP5/RBM3/DCLK1 signaling axis that critically propels PDAC progression, thereby nominating SEC14L2 as a compelling therapeutic target for this devastating disease.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148831086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

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