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While existing evidence indicates a plausible link between SMC4 and oncogenic manifestations, its precise role in the trajectory of prostate cancer remains ambiguous. The Cancer Genome Atlas (TCGA) database analysis reveals that aberrant expression of SMC4 exhibits a robust prognostic association with metastatic progression. To investigate the function of SMC4, the\n                    <jats:italic>SMC4<\/jats:italic>\n                    gene is knocked down in RM1\u2010LM cells, a highly metastatic cell clone is developed, using the CRISPR\/Cas9 system. The results show that SMC4 knockdown significantly diminished cell proliferation and migration in vitro. Furthermore, in a murine model, RM1\u2010LM cells display higher lung metastasis capabilities than SMC4 knockdown cells. SMC4 knockdown inhibited the activation of mTOR and downregulated the expression of Rheb. KEGG enrichment analyses of the RNA\u2010seq results reveal that cancer signaling pathways and metabolic pathways are enriched. The SMC4 interactome is uncovered through IP\u2010MS and indicates that SMC4 interacts with GLUT1, encoded by\n                    <jats:italic>Slc2a1<\/jats:italic>\n                    . Glycolytic rate assay illustrates that knocking down SMC4 inhibits the cell glycolysis rate and ATP production. Collectively, the data suggests that the interaction between SMC4 and GLUT1, as confirmed by co\u2010IP, promotes prostate cancer cell metastasis through the Rheb\/mTOR pathway.\n                  <\/jats:p>","DOI":"10.1002\/advs.202500369","type":"journal-article","created":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T10:03:35Z","timestamp":1745575415000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["SMC4 Promotes Prostate Cancer Cell Proliferation and Metastasis via the Rheb\/mTOR Pathway"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4017-0576","authenticated-orcid":false,"given":"Wei","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Medicine Southern University of\u00a0Science and\u00a0Technology  Shenzhen Guangdong 518053 China"},{"name":"Shenzhen Key Laboratory of Cardiovascular Health and Precision Medicine School of Public Health and Emergency Management Southern University of\u00a0Science and\u00a0Technology  Shenzhen Guangdong 518055 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyuan","family":"Qin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biotherapy and Cancer Center West China Hospital and West China School of Basic Medical Sciences &amp; Forensic Medicine and Collaborative Innovation Center for Biotherapy Sichuan University  Chengdu Sichuan 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaokang","family":"Li","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center Wuhan Jinxin Integrated Chinese and Western Medicine Obstetrics and Gynecology Hospital  Wuhan 430000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Chang","sequence":"additional","affiliation":[{"name":"Xiangyang Central Hospital Affiliated Hospital of Hubei University of Arts and Science  Xiangyang Hubei 441000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianzi","family":"Wei","sequence":"additional","affiliation":[{"name":"School of Medicine Southern University of\u00a0Science and\u00a0Technology  Shenzhen Guangdong 518053 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Medicine Southern University of\u00a0Science and\u00a0Technology  Shenzhen Guangdong 518053 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibo","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Shenzhen Institute of Respiratory Diseases First Affiliated Hospital of Southern University of Science and Technology Second Clinical Medical College of Jinan University  Shenzhen 518020 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Guo","sequence":"additional","affiliation":[{"name":"Center for Clinical Research and Innovation (CCRI) Shenzhen Hospital Southern Medical University  Shenzhen Guangdong 518101 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Medicine Southern University of\u00a0Science and\u00a0Technology  Shenzhen Guangdong 518053 China"},{"name":"Department of Human Cell Biology and Genetics Joint Laboratory of Guangdong\u2010Hong Kong Universities for Vascular Homeostasis and Diseases School of Medicine Southern University of Science and Technology  Shenzhen Guangdong 518101 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Medicine Southern University of\u00a0Science and\u00a0Technology  Shenzhen Guangdong 518053 China"},{"name":"Department of Human Cell Biology and Genetics Joint Laboratory of Guangdong\u2010Hong Kong Universities for Vascular Homeostasis and Diseases School of Medicine Southern University of Science and Technology  Shenzhen Guangdong 518101 China"},{"name":"SUSTech\u2010KCL School of Medicine Southern University of Science and Technology  Shenzhen Guangdong 518055 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,25]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21820"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2016.08.003"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1530\/JME-14-0203"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/35094009"},{"key":"e_1_2_9_5_1","first-page":"365","volume":"4","author":"Chandrasekar T.","year":"2015","journal-title":"Transl. 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