journal article·2025-06Open access

SMC4 Promotes Prostate Cancer Cell Proliferation and Metastasis via the Rheb/mTOR Pathway

Wei Zhang, Siyuan Qin, Xiaokang Li, Ming Chang, Tianzi Wei, Xin Huang, Haibo Tong, Xia Guo, Yi Lu, Jian Zhang

Advanced Science· Volume 12· Issue 23

Abstract

Abstract Structural maintenance of chromosome protein 4 (SMC4), is a key structural component of mitotic chromosomes. 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 SMC4 gene is knocked down in RM1‐LM 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‐LM 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‐seq results reveal that cancer signaling pathways and metabolic pathways are enriched. The SMC4 interactome is uncovered through IP‐MS and indicates that SMC4 interacts with GLUT1, encoded by Slc2a1 . 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‐IP, promotes prostate cancer cell metastasis through the Rheb/mTOR pathway.
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Research context

OpenAlex topics: Prostate Cancer Treatment and Research · Cancer, Lipids, and Metabolism · Cancer-related Molecular Pathways

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

School of Medicine Southern University of Science and Technology Shenzhen Guangdong 518053 China

Shenzhen Key Laboratory of Cardiovascular Health and Precision Medicine School of Public Health and Emergency Management Southern University of Science and Technology Shenzhen Guangdong 518055 China

State Key Laboratory of Biotherapy and Cancer Center West China Hospital and West China School of Basic Medical Sciences & Forensic Medicine and Collaborative Innovation Center for Biotherapy Sichuan University Chengdu Sichuan 610041 China

Reproductive Medicine Center Wuhan Jinxin Integrated Chinese and Western Medicine Obstetrics and Gynecology Hospital Wuhan 430000 China

Xiangyang Central Hospital Affiliated Hospital of Hubei University of Arts and Science Xiangyang Hubei 441000 China

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

Center for Clinical Research and Innovation (CCRI) Shenzhen Hospital Southern Medical University Shenzhen Guangdong 518101 China

Department of Human Cell Biology and Genetics Joint Laboratory of Guangdong‐Hong Kong Universities for Vascular Homeostasis and Diseases School of Medicine Southern University of Science and Technology Shenzhen Guangdong 518101 China

SUSTech‐KCL School of Medicine Southern University of Science and Technology Shenzhen Guangdong 518055 China

Funding

National Natural Science Foundation of China

References (38)

Show source-provided references
1. 10.3322/caac.2182010.3322/caac.21820 ↗
2. 10.1016/j.eururo.2016.08.00310.1016/j.eururo.2016.08.003 ↗
3. 10.1530/JME-14-020310.1530/JME-14-0203 ↗
4. 10.1038/3509400910.1038/35094009 ↗
5. Chandrasekar T. · Transl. Androl. Urol. · 2015 · 4 · 365
6. 10.3747/co.v17i0.71810.3747/co.v17i0.718 ↗
7. 10.7314/APJCP.2014.15.21.945910.7314/APJCP.2014.15.21.9459 ↗
8. 10.1101/gad.132050510.1101/gad.1320505 ↗
9. 10.1016/j.cell.2016.01.03310.1016/j.cell.2016.01.033 ↗
10. 10.1038/srep3450810.1038/srep34508 ↗
11. 10.3892/or.2012.192910.3892/or.2012.1929 ↗
12. 10.1002/cam4.30910.1002/cam4.309 ↗
13. 10.1186/1756-9966-33-5510.1186/1756-9966-33-55 ↗
14. 10.1038/oncsis.2017.810.1038/oncsis.2017.8 ↗
15. 10.1158/1078-0432.CCR-15-125010.1158/1078-0432.CCR-15-1250 ↗
16. 10.1016/j.cmet.2013.09.01310.1016/j.cmet.2013.09.013 ↗
17. 10.1002/ptr.708710.1002/ptr.7087 ↗
18. 10.2217/fon.10.3310.2217/fon.10.33 ↗
19. 10.1016/j.celrep.2020.01.03310.1016/j.celrep.2020.01.033 ↗
20. 10.1016/j.cell.2017.09.00810.1016/j.cell.2017.09.008 ↗
21. 10.1016/j.cmet.2023.07.00510.1016/j.cmet.2023.07.005 ↗
22. 10.1080/10428194.2017.138790610.1080/10428194.2017.1387906 ↗
23. 10.1155/2019/898370410.1155/2019/8983704 ↗
24. 10.1016/j.cmet.2017.08.01710.1016/j.cmet.2017.08.017 ↗
25. 10.1007/s00018-015-2098-510.1007/s00018-015-2098-5 ↗
26. 10.1158/1078-0432.CCR-13-227010.1158/1078-0432.CCR-13-2270 ↗
27. 10.2174/138920021666615101511235610.2174/1389200216666151015112356 ↗
28. 10.1088/1752-7163/aa51d610.1088/1752-7163/aa51d6 ↗
29. 10.1038/s41419-018-0367-610.1038/s41419-018-0367-6 ↗
30. 10.1158/0008-5472.CAN-19-178910.1158/0008-5472.CAN-19-1789 ↗
31. 10.1038/s41467-017-02733-410.1038/s41467-017-02733-4 ↗
32. 10.7314/APJCP.2013.14.8.485310.7314/APJCP.2013.14.8.4853 ↗
33. 10.1016/j.trsl.2014.12.00110.1016/j.trsl.2014.12.001 ↗
34. 10.1016/j.cell.2019.06.00510.1016/j.cell.2019.06.005 ↗
35. 10.1074/jbc.C00002320010.1074/jbc.C000023200 ↗
36. 10.1016/j.cell.2012.01.05810.1016/j.cell.2012.01.058 ↗
37. 10.15252/embj.201810029410.15252/embj.2018100294 ↗
38. 10.1038/s41598-017-05400-210.1038/s41598-017-05400-2 ↗