The FASEB Journal最新文献

{"title":"Correction to “Cysteine-rich protein 61 regulates adipocyte differentiation from mesenchymal stem cells through mammalian target of rapamycin complex 1 and canonical Wnt signaling”","authors":"","doi":"10.1096/fj.202501037","DOIUrl":"https://doi.org/10.1096/fj.202501037","url":null,"abstract":"<p>\u0000 <span>Yang, Y</span>, <span>Qi, Q</span>, <span>Wang, Y</span>, <span>Shi, Y</span>, <span>Yang, W</span>, <span>Cen, Y</span>, <span>Zhu, E</span>, <span>Li, X</span>, <span>Chen, D</span>, <span>Wang, B</span>. <span>Cysteine-rich protein 61 regulates adipocyte differentiation from mesenchymal stem cells through mammalian target of rapamycin complex 1 and canonical Wnt signaling</span>. <i>FASEB J.</i> <span>2018</span>; <span>32</span>(<span>6</span>): <span>3096</span>–<span>3107</span>. https://doi.org/10.1096/fj.201700830RR.\u0000 </p><p>Author Requested changes.</p><p>In the originally published article, due to the extensive volume of experimental data and an oversight on their part, errors occurred during the storage and retrieval of Western blot images and incorrect images were used for Figure 4E (images of β-catenin and β-actin), Figure 4F (image of mTOR), and Figure 5E (image of β-actin).</p><p>The authors apologize for any inconvenience caused by this oversight. The errors do not affect the results and conclusions published in the article.</p><p>The corrected Figure 4 and Figure 5 are presented below.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 7","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202501037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intracellular Sphingosine-1-Phosphate Induces Lipolysis Through Direct Activation of Protein Kinase C Zeta","authors":"Sarah Weske,&nbsp;Melissa Kim Nowak,&nbsp;Alex Zaufel,&nbsp;Lea Esser,&nbsp;Christoph Peter,&nbsp;Lisa Walz,&nbsp;Helena Kühn,&nbsp;Tsyon Wolde,&nbsp;Julia Hoppe,&nbsp;Nathalie Hannelore Schröder,&nbsp;Tobias Buschmann,&nbsp;Philipp Wollnitzke,&nbsp;Bodo Levkau","doi":"10.1096/fj.202403272R","DOIUrl":"https://doi.org/10.1096/fj.202403272R","url":null,"abstract":"<p>Dysregulated sphingosine-1-phosphate (S1P) signaling has been associated with obesity, insulin resistance, and type II diabetes. As metabolic disorders are intricately interrelated, studies on S1P effects explicitly on lipolysis have been scarce, particularly as S1P has also effects on adipogenesis, with studies implicating extracellular and intracellular mechanisms. Here, we have concentrated on the latter, as 10–50 μM S1P potently increased lipolysis in differentiated 3T3-L1 adipocytes, whereas S1P concentrations sufficient to activate S1P receptors (S1PRs; 0.1–1 μM) or S1PR agonists had no effect. Neither was ceramide increased by S1P, nor was S1P-mediated lipolysis affected by the ceramide synthase inhibitor Fumonisin B1. In contrast, inhibition of protein kinase C zeta (PKC zeta) completely abrogated S1P-mediated lipolysis. S1P also induced Thr410 phosphorylation of PKC zeta in 3T3-L1 adipocytes and activated recombinant PKC zeta in kinase assays. S1P-mediated lipolysis was dependent on hormone-sensitive lipase (HSL) and relied mechanistically on PKC zeta activation of MAPK to phosphorylate HSL at Ser660. Inhibition of S1P degradation by blocking the S1P lyase through VD-78 also increased lipolysis in 3T3-L1 cells and primary adipocytes. S1P lyase inhibition by 4-Deoxypyridoxine (DOP) in mice rendered obese by a 10-week high-fat diet (HFD) for an additional 6 weeks, concomitantly with the HFD, reduced white gonadal adipose tissue (gWAT) mass and diminished adipocyte size in gWAT and inguinal WAT, and increased free fatty acid in plasma and gWAT. PKC zeta phosphorylation and activity, as well as HSL Ser660 phosphorylation, were increased in gWAT of DOP-treated mice. This study assigns lipolysis as the first physiological function of PKC zeta activation by S1P and identifies an exclusive adipocyte-specific aspect of S1P function in obesity.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 7","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202403272R","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Mutations in Mig6 reduce inhibition of the epidermal growth factor receptor”","authors":"","doi":"10.1096/fj.202500971","DOIUrl":"https://doi.org/10.1096/fj.202500971","url":null,"abstract":"<p>\u0000 <span>Hayashi, S. Y.</span>, <span>Pak, S.</span>, <span>Torlentino, A.</span>, <span>Rizzo, R. C.</span>, <span>Miller, W. T.</span> (<span>2024</span>). <span>Mutations in Mig6 reduce inhibition of the epidermal growth factor receptor</span>. <i>The FASEB Journal</i> <span>38</span>(<span>22</span>): e70194, https://doi.org/10.1096/fj.202401330R.\u0000 </p><p>Author Requested the Changes.</p><p>1) In Figure 2B of the original manuscript, the middle column heading was K_D (nM). The correct heading should be K_D (μM).</p><p>2) In the Figure 2 legend, in the sentence that begins, “Fluorescence polarization...”, the wavelengths are incorrectly listed as 485 nM and 535 nM, rather than 485 nm and 535 nm (i.e., the letter m should not be capitalized).</p><p>No other modifications in the text, Figure 2A, or figure legend are needed.</p><p>The author apologizes for the two errors in Figure 2.</p><p>The corrected Figure 2B and legend are as follows:</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 7","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202500971","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SEMA6D modulates extracellular matrix metabolism in osteoarthritis by inhibiting the AGT/AGTR1a/IL-1β axis","authors":"Haoyu Yang,&nbsp;Xinjian Ye,&nbsp;JingJing Shang,&nbsp;Jiapei Yao,&nbsp;Yong Huang,&nbsp;Yaojun Lu,&nbsp;Xiaolong Lin,&nbsp;Gang Zhao,&nbsp;Xindie Zhou","doi":"10.1096/fj.202403120R","DOIUrl":"https://doi.org/10.1096/fj.202403120R","url":null,"abstract":"<p>The tissue-localized renin-angiotensin system (tRAS) plays a pivotal role in the crosstalk between cardiovascular factors and osteoarthritis (OA). Semaphorin 6D (SEMA6D), a cardiovascular neuroeffector, may contribute to chondrocyte homeostasis; however, its cartilage-specific functions remain unclear. Chondrocytes with altered SEMA6D expression were established via gene transfection. RNA sequencing was performed to identify SEMA6D-related genes and pathways, with preliminary validation in human OA samples. Furthermore, biochemical methods were employed to investigate the role of the AGT/AGTR1a/IL-1β axis in mediating SEMA6D-associated extracellular matrix metabolism (ECM). An AAV5-based lentiviral vector was used to generate OA rat models overexpressing SEMA6D, followed by radiological and histological analyses. SEMA6D overexpression significantly enhanced ECM homeostasis, marked by increased Aggrecan, COL2A1 and decreased COL10A1, MMP13, and Runx2 expression. These SEMA6D-induced genes were enriched in the tRAS pathway, with AGT, AGTR1a, and IL-1β identified as critical targets. Furthermore, the AGT/AGTR1a/IL-1β axis activated ECM degradation in chondrocytes, while SEMA6D overexpression effectively suppressed this signaling. In the OA rat model, elevated SEMA6D expression significantly reduced cartilage degradation. SEMA6D confers chondroprotective effects in OA by modulating the tRAS pathway, likely through inhibition of the AGT/AGTR1a/IL-1β axis, thereby regulating ECM metabolism and chondrocyte hypertrophy. These findings enhance our understanding of cardiovascular influences on cartilage health and reveal tissue-specific regulatory mechanisms in OA.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 7","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of inner nuclear membrane protein emerin in myogenesis","authors":"Nicholas Marano,&nbsp;James M. Holaska","doi":"10.1096/fj.202500323","DOIUrl":"https://doi.org/10.1096/fj.202500323","url":null,"abstract":"<p>Emerin, a ubiquitously expressed inner nuclear membrane protein, plays a central role in maintaining nuclear structure and genomic organization, and in regulating gene expression and cellular signaling pathways. These functions are critical for proper myogenic differentiation and are closely linked to the pathology of Emery-Dreifuss muscular dystrophy 1 (EDMD1), a laminopathy caused by mutations in the <i>EMD</i> gene. Emerin, along with other nuclear lamina proteins, modulates chromatin organization, cell signaling, gene expression, and cellular mechanotransduction, processes essential for muscle development and homeostasis. Loss of emerin function disrupts chromatin localization, causes dysregulated gene expression, and alters nucleoskeletal organization, resulting in impaired myogenic differentiation. Recent findings suggest that emerin tethers repressive chromatin at the nuclear envelope, a process essential for robust myogenesis. This review provides an in-depth discussion of emerin's multifaceted roles in nuclear organization, gene regulation, and cellular signaling, highlighting its importance in myogenic differentiation and disease progression.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 7","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202500323","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of proanthocyanidins in treating Type 2 diabetic osteoporosis via SIRT6/Nrf2/GPX4 pathways","authors":"Run-xun Ma,&nbsp;Bing-hao Lin,&nbsp;Si-xiang Feng,&nbsp;Yi-tian Bu,&nbsp;Zi-Hao Chen,&nbsp;Yi-xun Huang,&nbsp;En-Li Li,&nbsp;She-ji Weng,&nbsp;Lei Yang","doi":"10.1096/fj.202403032R","DOIUrl":"https://doi.org/10.1096/fj.202403032R","url":null,"abstract":"<p>This study investigates the therapeutic potential of proanthocyanidins (PAC) in addressing Type 2 diabetic osteoporosis (T2DOP) by activating the SIRT6/Nrf2/GPX4 signaling pathways. T2DOP is characterized by compromised bone structure and heightened oxidative stress, where ferroptosis plays a pivotal role. Utilizing a T2DOP mouse model and MC3T3-E1 cells under high glucose conditions, we evaluated the impact of PAC on bone health and iron homeostasis. Our results, obtained through micro-CT, histological staining, Western blot, and immunofluorescence analyses, revealed reductions in bone density and decreased GPX4 expression in T2DOP conditions, indicating ferroptosis and oxidative stress. However, PAC treatment improved trabecular bone structure, reduced bone marrow adipocytes, decreased oxidative stress, and enhanced expression of key osteogenic proteins. These findings highlight PAC's potential in mitigating T2DOP through the SIRT6/Nrf2/GPX4 pathways, offering promising therapeutic insights for managing diabetic osteoporosis.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 7","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Normal embryo development needs MEIG1-mediated sperm formation”","authors":"","doi":"10.1096/fj.202500897","DOIUrl":"https://doi.org/10.1096/fj.202500897","url":null,"abstract":"<p>Yi, Sheng, Yitian, Yap, Wei, Li et al. Normal embryo development needs MEIG1-mediated sperm formation. FASEB J. 2025 Mar 15;39(5): e70426. 10.1096/fj.202500109R. PMID: 40035530.</p><p>In the original publication of the article, the authors found the affiliation of the last author, Zhibing Zhang incorrect. They requested the correction.</p><p>The correct affiliation for Zhibing Zhang is as follows: Zhibing Zhang ^{2 5}.</p><p>2: Department of Physiology, School of Medicine, Wayne State University, Detroit, Michigan, USA;</p><p>5: Department of Obstetrics &amp; Gynecology, Wayne State University, Detroit, Michigan, USA.</p><p>The correct order of affiliation is as follows:</p><p>1 Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.</p><p>2 Department of Physiology, School of Medicine, Wayne State University, Detroit, Michigan, USA.</p><p>3 School of Nursing School of Public Health, Yangzhou University, Yangzhou, Jiangsu, China.</p><p>4 Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA.</p><p>5 Department of Obstetrics &amp; Gynecology, Wayne State University, Detroit, Michigan, USA.</p><p>6 Center for Molecular Medicine and Genetics, School of Medicine, Wayne State University, Detroit, Michigan, USA.</p><p>7 Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan, USA.</p><p>8 Department of Urology, University of Michigan, Ann Arbor, Michigan, USA.</p><p>Correct author list:</p><p>Yi Sheng ¹, Yi Tian Yap ², Wei Li ², Opeyemi Dhikhirullahi ², Changmin Niu ^{2 3}, Mashiat Rabbani ⁴, Stephen A Krawetz ^{5 6}, Saher Sue Hammoud ^{4 7 8}, Kyle E Orwig ¹, Zhibing Zhang ^{2 5}.</p><p>Authors apologize for this error.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 7","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202500897","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic analysis of liver fibrosis reveals EFEMP1 as a new modulator of focal adhesion and migration of hepatic stellate cells","authors":"Célia Thomas,&nbsp;Fidaa Bouezzedine,&nbsp;Dominique Bonnier,&nbsp;Vincent Legagneux,&nbsp;Nathalie Théret","doi":"10.1096/fj.202403086RR","DOIUrl":"https://doi.org/10.1096/fj.202403086RR","url":null,"abstract":"<p>Liver fibrosis is characterized by an excessive accumulation of extracellular matrix (ECM) leading to liver dysfunction. Proteomic approaches help to decipher ECM alterations during fibrosis progression. Using a decellularization method, we performed a proteomic analysis of 18 fibrotic human liver samples and identified 106 deregulated ECM proteins. Three members of the fibulin protein family (fibulin-2, -3, and -5) expressed by hepatic stellate cells were significantly associated with fibrosis progression. Integrative analyses of protein–protein interaction networks highlighted different functional annotations for these three fibulins. Gene silencing studies showed that unlike fibulin-2 (<i>FBLN2</i>), fibulin-3 (<i>EFEMP1</i>) depletion impaired focal adhesions, FAK phosphorylation, the fibronectin network, and cell migration. These findings are the first to demonstrate the critical involvement of fibulin-3 in the regulation of hepatic stellate cell focal adhesions and migration, emphasizing the intricate link between chronic liver disease progression and remodeling of the microenvironment.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 7","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202403086RR","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel feedback regulation loop of METTL11A–MAFG–NPL4 promotes bladder cancer cell proliferation and tumor progression","authors":"Bao-Sai Lu,&nbsp;Kai-Long Liu,&nbsp;Yue-Wei Yin,&nbsp;Yan-Ping Zhang,&nbsp;Jin-Chun Qi,&nbsp;Chen-Ming Zhao,&nbsp;Ya-Lin Niu,&nbsp;Ping-Ying Guo,&nbsp;Wei Li","doi":"10.1096/fj.202402830R","DOIUrl":"https://doi.org/10.1096/fj.202402830R","url":null,"abstract":"<p>Abnormal regulation of gene expression results in the malignant proliferation of bladder cancer (BC) cells. We previously demonstrated that NPL4 upregulation promotes BC progression; however, its regulatory and functional mechanisms on downstream genes in BC remain unknown. Transcriptome sequencing and reverse transcription–quantitative polymerase chain reaction were used to identify and confirm <i>METTL11A</i> as a downstream gene of NPL4. Protein interactions were detected through co-immunoprecipitation assays. Cell growth and tumor progression were assessed in vitro and in vivo using colony formation and MTS assays as well as xenograft animal models. Chromatin immunoprecipitation and luciferase activity assays were performed to investigate gene transcription regulation. We identified <i>METTL11A</i> as a downstream gene of NPL4, with its upregulation linked to poor outcomes in BC patients. METTL11A facilitates NPL4-regulated BC cell proliferation by promoting cyclin D1 expression. METTL11A enhances MAFG expression and contributes to METTL11A-mediated cell proliferation. Mechanistically, METTL11A interacts with MAFG, preventing its degradation through K6 methylation modification. MAFG and NRF2 bind to the promoter region of NPL4, promoting its transcription. Thus, the METTL11A–MAFG–NPL4 axis forms a positive feedback loop, promoting BC cell proliferation and tumor progression. Targeted inhibition of this regulatory loop could offer a novel therapeutic approach for BC.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 7","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"STEAP4 facilitates growth, migration, and invasion of prostate carcinoma through upregulation of NOTCH4","authors":"Shicheng Fan,&nbsp;Zhongyou Xia,&nbsp;Weijia Liu,&nbsp;Yuanquan Zhu,&nbsp;Xiaodong Liu,&nbsp;Peng Gu,&nbsp;Qingpeng Cui","doi":"10.1096/fj.202403129RR","DOIUrl":"https://doi.org/10.1096/fj.202403129RR","url":null,"abstract":"<p>STEAP4 manifested differential expression and aberrant methylation in prostate cancer (PCa). Therefore, this study proposed to explore the effect of STEAP4 on the PCa malignant phenotype in vivo and in vitro and the possible molecular mechanisms using RNA-seq. The expression of STEAP4 in PCa and its prognostic and diagnostic value was identified using bioinformatics. After exogenous modulation of STEAP4, the effect of STEAP4 on the malignant phenotype of PCa cells was examined using functional assays and nude mouse tumor models. The STEAP4-related differentially expressed genes (DEGs) and the hub genes were characterized using RNA-seq in conjunction with bioinformatics. STEAP4 exhibited high expression in PCa tissues from TCGA-PRAD and GEO datasets (GSE179321, GSE229904, and GSE237995), which predicted lower survival of patients. The STEAP4-associated nomogram model and diagnostic ROC curve had excellent predictive performance (AUC = 0.814). STEAP4 was overexpressed in PCa tissues and cells. Knockdown of STEAP4 effectively decreased the viability, number of invading cells, and wound healing of PCa cells and increased apoptosis. Overexpression of STEAP4 showed the opposite pattern. RNA-seq revealed that knockdown of STEAP4 resulted in 234 DEGs in PCa cells. <i>FGF17</i>, <i>KCNQ2</i>, <i>PDGFRB</i>, and <i>NOTCH4</i> are hub genes in DEGs. Notably, NOTCH4 was likewise overexpressed in PCa tissues and cells and was regulated by STEAP4. In in vitro experiments, overexpression of NOTCH4 facilitated PCa cell proliferation, migration, and invasion, which was limited by knockdown of STEAP4. In in vivo experiments, overexpression of STEAP4 exacerbated PCa tumor burden, which was rescued by knockdown of NOTCH4. STEAP4 is a valid biomarker for predicting prognosis and diagnosis of PCa patients. STEAP4 contributes to PCa growth, migration, and invasion by upregulating NOTCH4.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 7","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}