Oncogene最新文献

{"title":"Macrophage activation determines muscle wasting in pancreatic cancer.","authors":"Chia-Jung Chang, Po-Hsien Huang, Szu-Ying Chen, Pei-Chia Su, Li-Yun Ding, Ya-Chin Hou, Miao-Neng Hung, Kuan-Lin Chen, Ya-Na Wu, Shang-Rung Wu, Forn-Chia Lin, Pei-Jung Lu, Hsin-Yi Wu, Yu-Ju Chen, Chih-Han Chang, Chih-Peng Chang, Daw-Yang Hwang, Yi-Ching Wang, Yan-Shen Shan","doi":"10.1038/s41388-025-03434-9","DOIUrl":"https://doi.org/10.1038/s41388-025-03434-9","url":null,"abstract":"<p><p>The contribution of non-cancer tumoral microenvironment to cachexia is vastly unclear. Despite advances in understanding the signals involved in cancer cachexia progression, the exact time point of cachexia onset remains unpredictable. The transgenic Kras^LSL-G12D/+;Trp53^flox/flox;Pdx1-Cre (KP₂C) GEMM is a clinically relevant model, with the timing of cancer cachexia progression from the pre-cachectic, early-onset, to severe cachexia showed that the onset of cachexia was associated with differences in muscle wasting. The exact cell-of-origin in different types of non-cancer cells in the tumoral microenvironment and the circulating blood, which drives cachexia, remains unclear. Production of potent pro-cachectic substances that induce skeletal muscle wasting also requires mechanistic analysis. This study analyzed the PBMC and the mouse-derived syngeneic transplants (MDSTs) of KP₂C GEMM in recipient mice and pinpoints the cell-type changes with the timing of cachexia (>10% weight loss) by conducting single-cell expression analysis of cell-type-specific gene expression determinants of cachexia. Single-cell RNA sequencing analysis identified signals in high-quality, specific cell types of PBMC (29,615 cells) and MDST (23,151 cells). The scRNA-seq data identified differentially expressed chitinase 3 like 1 (CHI3L1 encoded by mouse Chi3l1) and chitinase-like 3 (CHI3L3, encoded by Chil3) and that macrophages are significant mediators of early-onset muscle wasting in tumor-bearing mice. C2C12 myoblasts treated with the CHI3L1 recombinant protein suppressed myotube formation and upregulated mRNA expression of Hdac3, Tlr9, Irf3, Tbk1, and Nfkb1. Skeletal muscle-specific conditional Hdac3 knockout in tumor-bearing mice decreased muscle wasting via CHI3L1-HDAC3 signaling. An anti-CHI3L1 monoclonal antibody was administered to target these macrophage populations, and the treatment resulted in suppressed tumor growth, metastatic progression, and protected body weight. Our results support the role of pancreatic tumor-associated macrophages in mediating skeletal muscle wasting and provide a clinically relevant mechanism of progression from the pre-cachectic state to the cachexia onset.</p>","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182972","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}

{"title":"Necrosis as a fundamental driver of loss of resilience and biological decline: what if we could intervene?","authors":"Carina Kern, Joseph V Bonventre, Alexander W Justin, Kianoush Kashani, Elizabeth Reynolds, Keith Siew, Bill Davis, Halime Karakoy, Nikodem Grzesiak, Damian Miles Bailey","doi":"10.1038/s41388-025-03431-y","DOIUrl":"https://doi.org/10.1038/s41388-025-03431-y","url":null,"abstract":"<p><p>Necrosis is uncontrolled cell death that marks the irreversible threshold of biological degeneration. Rooted in the Greek nekros (death), it is a pivotal mechanism underlying numerous diseases, including cancer, as well as renal, cardiac, neuronal, and hepatic disorders, and more broadly, the aging process. Despite its profound impact on morbidity and mortality, necrosis remains untreatable and has long been viewed as a chaotic, unavoidable aspect of biology. This review examines the mechanisms of necrosis and outlines its far-reaching impact on health, as revealed by emerging evidence. Furthermore, we explore its potential as a game-changing therapeutic target. Inhibiting necrosis could revolutionize treatments for acute and chronic age-related conditions like cancer, kidney disease, cardiovascular disease (including heart attacks and strokes), and neurodegeneration, while also preserving resilience-and even slowing aging itself. Beyond Earth, where microgravity, cosmic radiation, and oxidative stress accelerate cellular decline, targeting necrosis may also hold the key to preserving astronaut resilience and health on long-duration space missions, offering insights that could reshape human longevity both on and off the planet.</p>","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174314","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}

{"title":"Crosstalk between SUMOylation and ubiquitination controls the stability of transcription factor zinc finger protein 24: a novel antitumor mechanism in bladder cancer.","authors":"Xiaosong Wei, Beibei Wang, Yang Yang, Zhiwei Fang, Chengzhi Yi, Liuhui Zhang, Xin Fan, Dongdong Tang, Lirong Zhang, Xiaoming Yang, Dongkui Song","doi":"10.1038/s41388-025-03450-9","DOIUrl":"https://doi.org/10.1038/s41388-025-03450-9","url":null,"abstract":"<p><p>Zinc finger protein 24 (ZNF24) is a conserved multifunctional transcription factor associated with tumorigenesis, but its function in bladder carcinogenesis remains unclear. Herein, the expression of ZNF24 was decreased in bladder cancer (BC) cells and tissues, and patients with higher expression of ZNF24 had a better prognosis. Doxycycline-induced overexpression and knockdown of ZNF24 identified its anti-proliferative and anti-metastasis role in BC in vitro and in vivo. The potential genes for the anti-cancer role of ZNF24, involving transcriptional regulation of several factors, such as dual-specificity phosphatase 1 and squalene epoxidase. E2 conjugating enzyme UBC9 and small ubiquitin-like modifier (SUMO) 1 were found to interact with ZNF24, suggesting that ZNF24 may be SUMOylated. Consistent with the expression, ZNF24 SUMOylation levels were decreased in BC cells and tissues. Pan-SUMOylation inhibition promoted protein degradation of ZNF24. UBC9 SUMOylated ZNF24 at Lys-27 (K27) site with SUMO1 modification and the K27 mutation of ZNF24 greatly damaged the protein stability of ZNF24. Cullin 3 (CUL3), a E3 ubiquitin ligase, was responsible for the degradation of ZNF24. ZNF24 SUMOylation prevented CUL3-mediated protein degradation of ZNF24. Overall, the crosstalk between the SUMOylation and ubiquitination of ZNF24 may be a novel regulatory mechanism to block tumorigenesis and development of BC.</p>","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174311","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}

{"title":"BRD4 regulates PAI-1 expression in tumor-associated macrophages to drive chemoresistance in colorectal cancer.","authors":"Dun Pan, Jinfeng Hu, Guo Li, Xuming Gao, Jie Wang, Leisi Jiang, Hong Lin, Yulin Chen, Yanheng Chen, Yiran Zheng, Junjin Lin, Min Zheng, Hui Chen, Lin-Feng Chen, Xiangming Hu","doi":"10.1038/s41388-025-03453-6","DOIUrl":"https://doi.org/10.1038/s41388-025-03453-6","url":null,"abstract":"<p><p>Tumor-associated macrophages (TAMs) in the tumor microenvironment play a key role in drug resistance, but the mechanisms underlying TAM polarization and its role in drug resistance remain unclear. Here, we identified BRD4 as a critical factor in TAM polarization and drug resistance in colorectal cancer (CRC). BRD4 deficiency in macrophages impaired M2-like TAM polarization, and tumors from myeloid-lineage specific Brd4 conditional knockout (Brd4-CKO) mice displayed a reduction in infiltrating M2-like TAMs and an enhanced anti-tumor microenvironment. Colon cancer cells treated with conditioned medium from polarized Brd4-deficient TAMs, as well as tumors in Brd4-CKO mice, were more sensitive to oxaliplatin. RNA-seq and cytokine microarray analysis revealed that mRNA and protein levels of PAI-1 were significantly decreased in Brd4-deficient polarized TAMs. BRD4 was recruited to the promoter of Serpine1, promoting SMAD-dependent PAI-1 expression. Supplementing Brd4-deficient TAMs with recombinant PAI-1 hampered the sensitivity of colon cancer cells to oxaliplatin. Moreover, PAI-1 inhibitor and oxaliplatin synergistically suppressed the growth of colon tumors. Clinically, the expression levels of BRD4 in TAMs and PAI-1 in tumors were elevated in CRC patients with chemoresistance, correlating with shorter recurrence-free survival. Collectively, our findings uncover a novel role for BRD4 in TAM polarization and drug resistance via PAI-1 upregulation, suggesting the BRD4/PAI-1 axis as a potential prognostic marker and therapeutic target in CRC.</p>","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174396","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}

{"title":"P5CS deacetylation mediated by SIRT2 facilitates tumor growth by enhancing mitochondrial respiration in hepatocellular carcinoma.","authors":"Xiaofang Geng, Mengyao Li, Lu Zhang, Yihan Cai, Xin Chen, Xiayue Mu, Jie Wang, Bowen Liu","doi":"10.1038/s41388-025-03456-3","DOIUrl":"https://doi.org/10.1038/s41388-025-03456-3","url":null,"abstract":"<p><p>Cancer cells typically exhibit enhanced mitochondrial metabolism to fulfill their energy and biosynthetic demands for growth. The mitochondrial response to fluctuations in cellular energy demand is essential for cellular adaptation and proper organ function. The mitochondrial delta-1-pyrroline-5-carboxylate synthase (P5CS) encoded by the ALDH18A1 gene, the key enzyme for proline synthesis, is frequently up-regulated during tumor development. However, the regulatory mechanisms governing P5CS activity in the occurrence and development of hepatocellular carcinoma (HCC) remain largely unknown. In this study, we observe that P5CS is highly expressed in HCC tissues, and elevated levels of P5CS expression are associated with poor prognosis in HCC patients. Notably, the knockdown of P5CS inhibits the proliferation, migratory and invasive capabilities of HCC cells by reducing mitochondrial respiration. Furthermore, we demonstrate that SIRT2 interacts with P5CS and mediates the deacetylation of P5CS at lysines K311 and K347, thereby activating its enzymatic activity. Activated P5CS significantly enhances mitochondrial respiration, which supports the proliferation and tumorigenesis of HCC cells. In addition, SIRT2 knockdown inhibits the proliferation, migratory and invasive capabilities of HCC cells. These observations suggest that SIRT2-mediated P5CS deacetylation is a crucial signaling event through which cancer cells sustain mitochondrial respiration and promote HCC progression. This finding offers the potential for targeting SIRT2-mediated P5CS deacetylation as a therapeutic strategy for HCC.</p>","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144160738","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}

{"title":"Importin-alpha transports Norrin to the nucleus to promote proliferation and Notch signaling in glioblastoma stem cells.","authors":"Ahmed El-Sehemy, Nobuhiko Tachibana, Arturo Ortin-Martinez, Dene Ringuette, Étienne Coyaud, Brian Raught, Peter Dirks, Valerie A Wallace","doi":"10.1038/s41388-025-03427-8","DOIUrl":"https://doi.org/10.1038/s41388-025-03427-8","url":null,"abstract":"<p><p>Norrin, a secreted protein encoded by NDP gene, is recognized for its established role as a paracrine canonical Frizzled-4/Wnt ligand that mediates angiogenesis and barrier function in the brain. However, emerging evidence suggests that Norrin possesses Frizzled-4-independent functions, notably impacting Notch activation and proliferation of cancer stem cells. We conducted a BioID protein-proximity screen to identify Norrin-interacting proteins. Surprisingly, a significant proportion of the proteins we identified were nuclear. Through comprehensive tagging and proximity ligation assays, we demonstrate that Norrin is transported to the nucleus through KPNA2 (member of the Importin-alpha family). Subsequently, we demonstrate that KPNA2 loss of function in patient-derived primary glioblastoma stem cells results in a nuclear to cytoplasmic shift of Norrin distribution, and a complete abrogation of its function in stimulating Notch signaling and cellular proliferation. These results indicate that Norrin is actively transported into the nucleus to regulate vital signaling pathways and cellular functions.</p>","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144160725","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}

{"title":"m⁶A modification-dependent upregulation of WNT2 facilitates M2-like macrophage polarization and perpetuates malignant progression of nasopharyngeal carcinoma.","authors":"Qiling Tang, Lvyuan Li, Junshang Ge, Dan Wang, Hongke Qu, Jie Wu, Qian Wang, Zhouying Peng, Yongzhen Mo, Yumin Wang, Chunmei Fan, Qijia Yan, Pan Chen, He Huang, Wenjia Guo, Lei Shi, Zhaoyang Zeng, Wei Xiong","doi":"10.1038/s41388-025-03452-7","DOIUrl":"https://doi.org/10.1038/s41388-025-03452-7","url":null,"abstract":"<p><p>The development and progression of nasopharyngeal carcinoma (NPC) involves intricate interactions between tumor cells and other surrounding cells in the tumor microenvironment (TME). Tumor-associated macrophages (TAMs) play pivotal roles in the progression of NPC, but their interactions remain largely unexplored. In this study, we revealed that NPC promoted M2-like polarization of TAMs through enhanced synthesis and secretion of WNT2. These M2-type macrophages, in turn, significantly boosted the proliferation and metastasis of NPC. This vicious cycle perpetuated the malignant progression of NPC. Mechanistically, elevated m⁶A modification of WNT2 in NPC stabilized its mRNA and facilitated its protein expression, which is coordinately regulated by the m⁶A \"eraser\" ALKBH5 and the \"reader\" YTHDF1. NPC promoted M2-like polarization of macrophages by activating the FZD2/β-catenin signaling axis through paracrine WNT2. Furthermore, elevated WNT2 can also trigger the WNT/β-catenin signaling pathway in NPC cells through autocrine signaling, synergically contributing to NPC development. The research reveals that WNT2 is upregulated in an m⁶A modification-dependent manner and promotes M2-like macrophages polarization of TAMs and malignant progression of NPC. This discovery provides novel potential molecular markers and therapeutic targets for the diagnosis and treatment of NPC.</p>","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151306","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}

{"title":"Post-translational modifications in DNA damage repair: mechanisms underlying temozolomide resistance in glioblastoma.","authors":"Yike Chen, Kaikai Ding, Shuyu Zheng, Songting Gao, Xiaohui Xu, Haijian Wu, Fengqi Zhou, Yongjie Wang, Jinfang Xu, Chun Wang, Chenhan Ling, Jing Xu, Lin Wang, Qun Wu, Georgios Giamas, Gao Chen, Jianmin Zhang, Chenggang Yi, Jianxiong Ji","doi":"10.1038/s41388-025-03454-5","DOIUrl":"https://doi.org/10.1038/s41388-025-03454-5","url":null,"abstract":"<p><p>Temozolomide (TMZ) resistance is one of the critical factors contributing to the poor prognosis of glioblastoma (GBM). As a first-line chemotherapeutic agent for GBM, TMZ exerts its cytotoxic effects through DNA alkylation. However, its therapeutic efficacy is significantly compromised by enhanced DNA damage repair (DDR) mechanisms in GBM cells. Although several DDR-targeting drugs have been developed, their clinical outcomes remain suboptimal. Post-translational modifications (PTMs) in GBM cells play a pivotal role in maintaining the genomic stability of DDR mechanisms, including methylguanine-DNA methyltransferase-mediated repair, DNA mismatch repair dysfunction, base excision repair, and double-strand break repair. This review focuses on elucidating the regulatory roles of PTMs in the intrinsic mechanisms underlying TMZ resistance in GBM. Furthermore, we explore the feasibility of enhancing TMZ-induced cytotoxicity by targeting PTM-related enzymatic to disrupt key steps in PTM-mediated DDR pathways. By integrating current preclinical insights and clinical challenges, this work highlights the potential of modulating PTM-driven networks as a novel therapeutic strategy to overcome TMZ resistance and improve treatment outcomes for GBM patients.</p>","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151309","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}

{"title":"Cancer-associated loss-of-function mutations in KCNQ1 enhance Wnt/β-catenin signalling disrupting epithelial homeostasis.","authors":"Camille Berenguier, Xingyu Chen, Benoit Allegrini, Hélène Guizouarn, Franck Borgese, Catherine Etchebest, Olivier Soriani, Raphael Rapetti-Mauss","doi":"10.1038/s41388-025-03447-4","DOIUrl":"https://doi.org/10.1038/s41388-025-03447-4","url":null,"abstract":"<p><p>Ion channels are emerging as regulators of intracellular signalling pathway, yet the molecular mechanisms underlying this role remain poorly understood. KCNQ1, a potassium channel with tumour suppressor functions, restricts Wnt/β-catenin signalling, a pathway whose dysregulation, often driven by protein-altering mutations, is a hallmark of several epithelial cancers. Here, we identify loss-of-function (LOF) mutations in KCNQ1 across multiple epithelial cancers and elucidate their impact on Wnt/β-catenin signalling. Our findings reveal that cancer-associated KCNQ1-LOF mutations regulate the β-catenin pathway through a dual mechanism. First, they drive β-catenin transcriptional activity through triggering MET receptor, bypassing Frizzled/LRP6 receptor complex activation. Second, these mutations suppress the expression of key negative regulators of Wnt signalling, such as DKK-1, Wif-1 and NKD-1, leading to amplified pathway activation in response to Wnt ligand stimulation. This dysregulation disrupts epithelial homeostasis, as demonstrated by impaired crypt organization and increased proliferation in mouse colon-derived organoids. Together, these findings uncover an original mechanism linking KCNQ1 dysfunction to aberrant Wnt/β-catenin signalling, highlighting the role of ion channels in regulating epithelial signalling networks and tissue homeostasis.</p>","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132548","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}

{"title":"Erk1^R84H is an oncoprotein that causes hepatocellular carcinoma in mice and imposes a rigorous negative feedback loop.","authors":"Nadine Soudah, Alexey Baskin, Merav Darash-Yahana, Ilona Darlyuk-Saadon, Karina Smorodinsky-Atias, Tali Shalit, Wei-Ping Yu, Alon Savidor, Eli Pikarsky, David Engelberg","doi":"10.1038/s41388-025-03437-6","DOIUrl":"https://doi.org/10.1038/s41388-025-03437-6","url":null,"abstract":"<p><p>The receptor tyrosine kinase (RTK)-Ras-Raf-MEK-Erk cascade is frequently mutated in cancer, but it is not known whether Erk is a sole mediator of the pathway's oncogenicity, and what degree of Erk activity is required for oncogenicity. Also, it is assumed that high Erk activity is required to impose and maintain oncogenicity, but the exact degree of required activity is not clear. We report that induced expression of the intrinsically active variant Erk1^R84H in mouse liver gave rise to hepatocellular carcinoma (HCC). Intriguingly, the phosphorylated/active form of Erk1^R84H was dramatically downregulated during HCC development, and became almost undetectable in mature tumors. Similarly, in Erk1^R84H-transformed NIH3T3 cells, the phosphorylated/active form of Erk1^R84H was undetectable. Thus, 1) Erk1 could by itself cause HCC in mice, suggesting that it is the major or even the sole mediator of the cascade's oncogenicity. 2) Erk1^R84H-induced tumors (and other tumors) are maintained by a minimal Erk activity. 3) Erk1^R84H is probably the driver of the malignancy in patients that carry the R84H mutation.</p>","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111651","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}