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SOCS1 depletion drives osteosarcoma stemness and chemoresistance by suppressing ACTN4 degradation

Acta Pharmacologica Sinica (2025)Cite this article

Abstract

Chemoresistance is a major factor contributing to the poor prognosis of osteosarcoma. Increasing evidence underscores the pivotal role of enhanced tumor stemness in driving drug resistance. In this study we investigated the molecular mechanisms underlying the chemoresistance and stemness in osteosarcoma. Two cisplatin-resistant osteosarcoma cell line models (U2OS-DDPr and 143B-DDPr) were established by culturing parental U2OS and 143B cells with escalating cisplatin concentrations (250 ng/mL to 2.5 µg/mL) over a 6-month period. We found that the expression levels of suppressor of cytokine signaling 1 (SOCS1), an E3 ubiquitin ligase, were markedly downregulated in both chemo-resistant osteosarcoma cells and osteosarcoma tumor specimens, and the reduced expression in tumor specimens was correlated to poor prognosis in osteosarcoma patients. Silencing SOCS1 significantly reduced cisplatin sensitivity, enhanced spheroid formation capacity, and upregulated the expression of stem cell markers including SOX2, OCT4, and CD44. Conversely, restoring SOCS1 expression reversed these effects both in vitro and in vivo. Immunoprecipitation-mass spectrometry analysis revealed that SOCS1 bound to ACTN4 and suppressed its protein expression by promoting K63-linked ubiquitination, ultimately leading to proteasomal degradation. Specifically, the SH2 domain of SOCS1 interacted with the N-terminal region of ACTN4, with Lys66 of ACTN4 playing a critical role in facilitating this interaction and subsequent ubiquitination. In addition, the expression of ACTN4 was highly enriched in chemo-resistant tissues, and its overexpression was positively associated with advanced tumor staging. Importantly, ACTN4 functioned as an oncogene to promote cisplatin resistance and stemness in osteosarcoma. Furthermore, we found that wortmannin, an inhibitor of ACTN4, could markedly block the effect of SOCS1 silencing on osteosarcoma aggressiveness. In conclusion, SOCS1 deletion promotes stemness and chemoresistance in osteosarcoma by inhibiting ACTN4 ubiquitination and degradation, which offers promising therapeutic targets for potentiating chemosensitivity in osteosarcoma.

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Fig. 1: SOCS1 is downregulated in chemo-resistant osteosarcoma and its low expression predicts poor prognosis.
Fig. 2: SOCS1 depletion enhances chemoresistance of osteosarcoma in vitro.
Fig. 3: SOCS1 silencing promotes osteosarcoma stemness and chemoresistance in vivo.
Fig. 4: SOCS1 physically interacts with ACTN4 in osteosarcoma cells.
Fig. 5: SOCS1 induces degradation of ACTN4 through ubiquitination.
Fig. 6: Higher expression of ACTN4 is potentially crucial for cisplatin resistance and predicts poor prognosis of osteosarcoma.
Fig. 7: ACTN4 inhibition attenuates chemoresistance and stemness in osteosarcoma.
Fig. 8: SOCS1 depletion drives chemoresistance and stemness through upregulating ACTN4.
Fig. 9: A schematic model showing the mechanism by which SOCS1 depletion drives the stemness and chemoresistance by upregulating ACTN4 in osteosarcoma.

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References

  1. Beird HC, Bielack SS, Flanagan AM, Gill J, Heymann D, Janeway KA, et al. Osteosarcoma. Nat Rev Dis Prim. 2022;8:77.

    Article  PubMed  Google Scholar 

  2. Meltzer PS, Helman LJ. New horizons in the treatment of osteosarcoma. N Engl J Med. 2021;385:2066–76.

    Article  PubMed  CAS  Google Scholar 

  3. Gill J, Gorlick R. Advancing therapy for osteosarcoma. Nat Rev Clin Oncol. 2021;18:609–24.

    Article  PubMed  Google Scholar 

  4. Loh JJ, Ma S. Hallmarks of cancer stemness. Cell Stem Cell. 2024;31:617–39.

    Article  PubMed  CAS  Google Scholar 

  5. Nguyen LV, Vanner R, Dirks P, Eaves CJ. Cancer stem cells: an evolving concept. Nat Rev Cancer. 2012;12:133–43.

    Article  PubMed  CAS  Google Scholar 

  6. Pan G, Liu Y, Shang L, Zhou F, Yang S. EMT-associated microRNAs and their roles in cancer stemness and drug resistance. Cancer Commun. 2021;41:199–217.

    Article  Google Scholar 

  7. Brown HK, Tellez-Gabriel M, Heymann D. Cancer stem cells in osteosarcoma. Cancer Lett. 2017;386:189–95.

    Article  PubMed  CAS  Google Scholar 

  8. Lin YH, Jewell BE, Gingold J, Lu L, Zhao R, Wang LL, et al. Osteosarcoma: molecular pathogenesis and iPSC modeling. Trends Mol Med. 2017;23:737–55.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Chen XP, Losman JA, Rothman P. SOCS proteins, regulators of intracellular signaling. Immunity. 2000;13:287–90.

    Article  PubMed  CAS  Google Scholar 

  10. Calvisi DF, Ladu S, Gorden A, Farina M, Conner EA, Lee JS, et al. Ubiquitous activation of Ras and Jak/Stat pathways in human HCC. Gastroenterology. 2006;130:1117–28.

    Article  PubMed  CAS  Google Scholar 

  11. Starr R, Willson TA, Viney EM, Murray LJ, Rayner JR, Jenkins BJ, et al. A family of cytokine-inducible inhibitors of signalling. Nature. 1997;387:917–21.

    Article  PubMed  CAS  Google Scholar 

  12. Palmer DC, Restifo NP. Suppressors of cytokine signaling (SOCS) in T cell differentiation, maturation, and function. Trends Immunol. 2009;30:592–602.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Baker BJ, Akhtar LN, Benveniste EN. SOCS1 and SOCS3 in the control of CNS immunity. Trends Immunol. 2009;30:392–400.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Zhang JG, Farley A, Nicholson SE, Willson TA, Zugaro LM, Simpson RJ, et al. The conserved SOCS box motif in suppressors of cytokine signaling binds to elongins B and C and may couple bound proteins to proteasomal degradation. Proc Natl Acad Sci USA. 1999;96:2071–6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Zhuang J, Shen L, Li M, Sun J, Hao J, Li J, et al. Cancer-associated fibroblast-derived miR-146a-5p generates a niche that promotes bladder cancer stemness and chemoresistance. Cancer Res. 2023;83:1611–27.

    Article  PubMed  CAS  Google Scholar 

  16. Chen CY, Tsay W, Tang JL, Shen HL, Lin SW, Huang SY, et al. SOCS1 methylation in patients with newly diagnosed acute myeloid leukemia. Genes Chromosomes Cancer. 2003;37:300–5.

    Article  PubMed  CAS  Google Scholar 

  17. Galm O, Yoshikawa H, Esteller M, Osieka R, Herman JG. SOCS-1, a negative regulator of cytokine signaling, is frequently silenced by methylation in multiple myeloma. Blood. 2003;101:2784–8.

    Article  PubMed  CAS  Google Scholar 

  18. Ohkawa K. Suppressor of cytokine signaling 1, a newly proposed tumor suppressor gene associated with hepatocellular carcinoma. J Gastroenterol. 2004;39:598–600.

    Article  PubMed  Google Scholar 

  19. Rottapel R, Ilangumaran S, Neale C, La Rose J, Ho JM, Nguyen MH, et al. The tumor suppressor activity of SOCS-1. Oncogene. 2002;21:4351–62.

    Article  PubMed  CAS  Google Scholar 

  20. Kishimoto T, Kikutani H. Knocking the SOCS off a tumor suppressor. Nat Genet. 2001;28:4–5.

    Article  PubMed  CAS  Google Scholar 

  21. Calabrese V, Mallette FA, Deschenes-Simard X, Ramanathan S, Gagnon J, Moores A, et al. SOCS1 links cytokine signaling to p53 and senescence. Mol Cell. 2009;36:754–67.

    Article  PubMed  CAS  Google Scholar 

  22. Yeganeh M, Gui Y, Kandhi R, Bobbala D, Tobelaim WS, Saucier C, et al. Suppressor of cytokine signaling 1-dependent regulation of the expression and oncogenic functions of p21(CIP1/WAF1) in the liver. Oncogene. 2016;35:4200–11.

    Article  PubMed  CAS  Google Scholar 

  23. Li Z, Metze D, Nashan D, Muller-Tidow C, Serve HL, Poremba C, et al. Expression of SOCS-1, suppressor of cytokine signalling-1, in human melanoma. J Invest Dermatol. 2004;123:737–45.

    Article  PubMed  CAS  Google Scholar 

  24. Huang FJ, Steeg PS, Price JE, Chiu WT, Chou PC, Xie K, et al. Molecular basis for the critical role of suppressor of cytokine signaling-1 in melanoma brain metastasis. Cancer Res. 2008;68:9634–42.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Sjoblom B, Salmazo A, Djinovic-Carugo K. Alpha-actinin structure and regulation. Cell Mol Life Sci. 2008;65:2688–701.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Miyanaga A, Honda K, Tsuta K, Masuda M, Yamaguchi U, Fujii G, et al. Diagnostic and prognostic significance of the alternatively spliced ACTN4 variant in high-grade neuroendocrine pulmonary tumours. Ann Oncol. 2013;24:84–90.

    Article  PubMed  CAS  Google Scholar 

  27. Thomas DG, Robinson DN. The fifth sense: Mechanosensory regulation of alpha-actinin-4 and its relevance for cancer metastasis. Semin Cell Dev Biol. 2017;71:68–74.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Tentler D, Lomert E, Novitskaya K, Barlev NA. Role of ACTN4 in tumorigenesis, metastasis, and EMT. Cells. 2019;8:1427.

  29. Honda K, Yamada T, Hayashida Y, Idogawa M, Sato S, Hasegawa F, et al. Actinin-4 increases cell motility and promotes lymph node metastasis of colorectal cancer. Gastroenterology. 2005;128:51–62.

    Article  PubMed  CAS  Google Scholar 

  30. An HT, Yoo S, Ko J. alpha-Actinin-4 induces the epithelial-to-mesenchymal transition and tumorigenesis via regulation of Snail expression and beta-catenin stabilization in cervical cancer. Oncogene. 2016;35:5893–904.

    Article  PubMed  CAS  Google Scholar 

  31. Yamamoto S, Tsuda H, Honda K, Onozato K, Takano M, Tamai S, et al. Actinin-4 gene amplification in ovarian cancer: a candidate oncogene associated with poor patient prognosis and tumor chemoresistance. Mod Pathol. 2009;22:499–507.

    Article  PubMed  CAS  Google Scholar 

  32. Jung J, Kim S, An HT, Ko J. alpha-Actinin-4 regulates cancer stem cell properties and chemoresistance in cervical cancer. Carcinogenesis. 2020;41:940–9.

    Article  PubMed  CAS  Google Scholar 

  33. Zhu M, Huang F, Sun H, Liu K, Chen Z, Yu B, et al. Characterization of ACTN4 as a novel antiviral target against SARS-CoV-2. Signal Transduct Target Ther. 2024;9:243.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Sharma S, Mayank AK, Nailwal H, Tripathi S, Patel JR, Bowzard JB, et al. Influenza A viral nucleoprotein interacts with cytoskeleton scaffolding protein alpha-actinin-4 for viral replication. FEBS J. 2014;281:2899–914.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Cheng M, Cao H, Yao P, Guan J, Wu P, Ji H, et al. PHF23 promotes NSCLC proliferation, metastasis, and chemoresistance via stabilization of ACTN4 and activation of the ERK pathway. Cell Death Dis. 2023;14:558.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Kile BT, Schulman BA, Alexander WS, Nicola NA, Martin HM, Hilton DJ. The SOCS box: a tale of destruction and degradation. Trends Biochem Sci. 2002;27:235–41.

    Article  PubMed  CAS  Google Scholar 

  37. Kamura T, Maenaka K, Kotoshiba S, Matsumoto M, Kohda D, Conaway RC, et al. VHL-box and SOCS-box domains determine binding specificity for Cul2-Rbx1 and Cul5-Rbx2 modules of ubiquitin ligases. Genes Dev. 2004;18:3055–65.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Anwar MA, El-Baba C, Elnaggar MH, Elkholy YO, Mottawea M, Johar D, et al. Novel therapeutic strategies for spinal osteosarcomas. Semin Cancer Biol. 2020;64:83–92.

    Article  PubMed  CAS  Google Scholar 

  39. Mu H, Zuo D, Chen J, Liu Z, Wang Z, Yang L, et al. Detection and surveillance of circulating tumor cells in osteosarcoma for predicting therapy response and prognosis. Cancer Biol Med. 2022;19:1397–409.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Kansara M, Teng MW, Smyth MJ, Thomas DM. Translational biology of osteosarcoma. Nat Rev Cancer. 2014;14:722–35.

    Article  PubMed  CAS  Google Scholar 

  41. Wei X, Feng J, Chen L, Zhang C, Liu Y, Zhang Y, et al. METTL3-mediated m6A modification of LINC00520 confers glycolysis and chemoresistance in osteosarcoma via suppressing ubiquitination of ENO1. Cancer Lett. 2024;611:217194.

  42. Korholz J, Chen LS, Strauss T, Schuetz C, Dalpke AH. One gene to rule them all - clinical perspectives of a potent suppressor of cytokine signaling - SOCS1. Front Immunol. 2024;15:1385190.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Yoshikawa H, Matsubara K, Qian GS, Jackson P, Groopman JD, Manning JE, et al. SOCS-1, a negative regulator of the JAK/STAT pathway, is silenced by methylation in human hepatocellular carcinoma and shows growth-suppression activity. Nat Genet. 2001;28:29–35.

    Article  PubMed  CAS  Google Scholar 

  44. Beaurivage C, Champagne A, Tobelaim WS, Pomerleau V, Menendez A, Saucier C. SOCS1 in cancer: an oncogene and a tumor suppressor. Cytokine. 2016;82:87–94.

    Article  PubMed  CAS  Google Scholar 

  45. Lin L, Chen S, Wang H, Gao B, Kallakury B, Bhuvaneshwar K, et al. SPTBN1 inhibits inflammatory responses and hepatocarcinogenesis via the stabilization of SOCS1 and downregulation of p65 in hepatocellular carcinoma. Theranostics. 2021;11:4232–50.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Gong HL, Tao Y, Mao XZ, Song DY, You D, Ni JD. MicroRNA-29a suppresses the invasion and migration of osteosarcoma cells by regulating the SOCS1/NF-kappaB signaling pathway through negatively targeting DNMT3B. Int J Mol Med. 2019;44:1219–32.

    PubMed  PubMed Central  CAS  Google Scholar 

  47. Chen D, Bao C, Zhao F, Yu H, Zhong G, Xu L, et al. Exploring specific miRNA-mRNA axes with relationship to taxanes-resistance in breast cancer. Front Oncol. 2020;10:1397.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Ouyang S, Li H, Lou L, Huang Q, Zhang Z, Mo J, et al. Inhibition of STAT3-ferroptosis negative regulatory axis suppresses tumor growth and alleviates chemoresistance in gastric cancer. Redox Biol. 2022;52:102317.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Zitzmann K, Brand S, De Toni EN, Baehs S, Goke B, Meinecke J, et al. SOCS1 silencing enhances antitumor activity of type I IFNs by regulating apoptosis in neuroendocrine tumor cells. Cancer Res. 2007;67:5025–32.

    Article  PubMed  CAS  Google Scholar 

  50. Yang C, Li Y, Yang Y, Ni Q, Zhang Z, Chai Y, et al. Synthetic high-density lipoprotein-based nanomedicine to silence SOCS1 in tumor microenvironment and trigger antitumor immunity against glioma. Angew Chem Int Ed Engl. 2023;62:e202312603.

    Article  PubMed  CAS  Google Scholar 

  51. Sun H, Li H, Guan Y, Yuan Y, Xu C, Fu D, et al. BICC1 drives pancreatic cancer stemness and chemoresistance by facilitating tryptophan metabolism. Sci Adv. 2024;10:eadj8650.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Mu M, Zhang Q, Li J, Zhao C, Li X, Chen Z, et al. USP51 facilitates colorectal cancer stemness and chemoresistance by forming a positive feed-forward loop with HIF1A. Cell Death Differ. 2023;30:2393–407.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Perkins RS, Murray G, Suthon S, Davis L, Perkins NB 3rd, Fletcher L, et al. WNT5B drives osteosarcoma stemness, chemoresistance and metastasis. Clin Transl Med. 2024;14:e1670.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Lou L, Deng T, Yuan Q, Wang L, Wang Z, Li X. Targeted silencing of SOCS1 by DNMT1 promotes stemness of human liver cancer stem-like cells. Cancer Cell Int. 2024;24:206.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Liau NPD, Laktyushin A, Lucet IS, Murphy JM, Yao S, Whitlock E, et al. The molecular basis of JAK/STAT inhibition by SOCS1. Nat Commun. 2018;9:1558.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Miao M, Pan M, Chen X, Shen J, Zhang L, Feng X, et al. IL-13 facilitates ferroptotic death in asthmatic epithelial cells via SOCS1-mediated ubiquitinated degradation of SLC7A11. Redox Biol. 2024;71:103100.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Wymann MP, Bulgarelli-Leva G, Zvelebil MJ, Pirola L, Vanhaesebroeck B, Waterfield MD, et al. Wortmannin inactivates phosphoinositide 3-kinase by covalent modification of Lys-802, a residue involved in the phosphate transfer reaction. Mol Cell Biol. 1996;16:1722–33.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Walker EH, Pacold ME, Perisic O, Stephens L, Hawkins PT, Wymann MP, et al. Structural determinants of phosphoinositide 3-kinase inhibition by wortmannin, LY294002, quercetin, myricetin, and staurosporine. Mol Cell. 2000;6:909–19.

    Article  PubMed  CAS  Google Scholar 

  59. Brunn GJ, Williams J, Sabers C, Wiederrecht G, Lawrence JC Jr., Abraham RT. Direct inhibition of the signaling functions of the mammalian target of rapamycin by the phosphoinositide 3-kinase inhibitors, wortmannin and LY294002. EMBO J. 1996;15:5256–67.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Sarkaria JN, Tibbetts RS, Busby EC, Kennedy AP, Hill DE, Abraham RT. Inhibition of phosphoinositide 3-kinase related kinases by the radiosensitizing agent wortmannin. Cancer Res. 1998;58:4375–82.

    PubMed  CAS  Google Scholar 

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Acknowledgements

We thank the public database for providing data for our research. This work was supported by the National Natural Science Foundation of China (82303076 and 82472905), National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine (QZ23-10) and the Science & Technology Development Fund of Tianjin Education Commission for Higher Education (2022KJ225).

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  1. These authors contributed equally: Jin-yan Feng, Xian-fu Wei, Long Chen

Authors and Affiliations

  1. National Key Laboratory of Draggability Evaluation and Systematic Translational Medicine, Tianjin’s Clinical Research Center for Cancer, Department of Bone and Soft Tissue Tumors, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, 300060, China

    Jin-yan Feng, Xian-fu Wei, Long Chen, Hou-zhi Yang, Yi-qin Li, Jin-wu Wang, Yong-heng Liu, Yao Xu, Qing-qian Zhao, Guo-wen Wang & Xiu-xin Han

  2. Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, 250012, China

    Xian-fu Wei

  3. Department of Gynecology, Tianjin Central Hospital of Obstetrics and Gynaecology, Tianjin, 300060, China

    Pu Li

  4. National Key Laboratory of Draggability Evaluation and Systematic Translational Medicine, Tianjin’s Clinical Research Center for Cancer, Department of Gastrointestinal Cancer Biology, Tianjin Cancer Institute, Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Tianjin, 300060, China

    Xiao-dong Zhang

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Contributions

XXH, GWW and XDZ conceptualized and designed the study. PL provided expert guidance in molecular docking and other experimental revisions during manuscript refinement. JYF, XFW and LC performed the major experiments. XFW, LC and HZY constructed the mouse model and performed the related assays. LC, YQL, and QQZ collected clinical information and performed clinical data analysis. YHL, JWW and YX performed bioinformatics and statistical analysis. JYF, XFW and LC designed and finalized the tables and figures. JYF and XFW wrote and revised the manuscript. All authors read and approved the manuscript.

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Correspondence to Pu Li, Xiao-dong Zhang, Guo-wen Wang or Xiu-xin Han.

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Feng, Jy., Wei, Xf., Chen, L. et al. SOCS1 depletion drives osteosarcoma stemness and chemoresistance by suppressing ACTN4 degradation. Acta Pharmacol Sin (2025). https://doi.org/10.1038/s41401-025-01650-3

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