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Article

Knockdown of STIP1 inhibits the invasion of CD133‑positive cancer stem‑like cells of the osteosarcoma MG63 cell line via the PI3K/Akt and ERK1/2 pathways

  • Authors:
    • Jian‑Hua Wang
    • Chen Gong
    • Feng‑Jin Guo
    • Xiao Zhou
    • Ming‑Sheng Zhang
    • Hong Qiu
    • Teng‑Fei Chao
    • Yang Liu
    • Liang Qin
    • Hui‑Hua Xiong
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China, Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
  • Pages: 2251-2259
    |
    Published online on: October 21, 2020
       https://doi.org/10.3892/ijmm.2020.4764
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Abstract

Osteosarcoma is the most common primary malignant tumor of the bone in adolescents and children, with high rates of metastasis and a poor prognosis. Recently, osteosarcoma cancer stem/stem‑like cells (CSCs) have been identified as the main cause of recurrence and metastasis. Stress‑induced phosphoprotein 1 (STIP1), a co‑chaperone that binds to heat shock proteins 70 and 90, is abnormally expressed in several tumor cell lines, and may play an important role in tumor cell migration and invasion. These features indicate that STIP1 may represent a new therapeutic target for osteosarcoma CSCs. However, the role of STIP1 in osteosarcoma CSC migration and invasion remains largely unknown. In the present study, CD133‑positive osteosarcoma CSCs were first isolated and cultured by magnetic cell sorting and serum‑free medium suspension cell sphere culture, respectively. Knockdown of STIP1 by small interfering RNA significantly was then shown to inhibit the migration and invasion of these cells, possibly due to the regulation of the expression of matrix metalloproteinase (MMP)‑2, MMP‑9 and tissue inhibitor of metalloproteinase‑2. Furthermore, data from the present study suggested that the knockdown of STIP1 decreased the levels of phosphorylated Akt and phosphorylated ERK1/2. In summary, these findings indicate that targeting STIP1 in osteosarcoma may constitute a viable molecular targeted therapy strategy for the inhibition of CSC invasion and migration.
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1 

Heare T, Hensley MA and Dell'Orfano S: Bone tumors: Osteosarcoma and Ewing's sarcoma. Curr Opin Pediatr. 21:365–372. 2009. View Article : Google Scholar : PubMed/NCBI

2 

Xiao X, Wang W, Li Y, Yang D, Li X, Shen C, Liu Y, Ke X, Guo S and Guo Z: HSP90AA1-mediated autophagy promotes drug resistance in osteosarcoma. J Exp Clin Cancer Res. 37:2012018. View Article : Google Scholar : PubMed/NCBI

3 

Ellis RJ: Molecular chaperones: Assisting assembly in addition to folding. Trends Biochem Sci. 31:395–401. 2006. View Article : Google Scholar : PubMed/NCBI

4 

Wang Y and McAlpine SR: Regulating the cytoprotective response in cancer cells using simultaneous inhibition of Hsp90 and Hsp70. Org Biomol Chem. 13:2108–2116. 2015. View Article : Google Scholar

5 

Longshaw VM, Baxter M, Prewitz M and Blatch GL: Knockdown of the co-chaperone Hop promotes extranuclear accumulation of Stat3 in mouse embryonic stem cells. Eur J Cell Biol. 88:153–166. 2009. View Article : Google Scholar

6 

Longshaw VM, Chapple JP, Balda MS, Cheetham ME and Blatch GL: Nuclear translocation of the Hsp70/Hsp90 organizing protein mSTI1 is regulated by cell cycle kinases. J Cell Sci. 117(Pt 5): 701–710. 2004. View Article : Google Scholar : PubMed/NCBI

7 

Zhai E, Liang W, Lin Y, Huang L, He X, Cai S, Chen J, Zhang N, Li J, Zhang Q, et al: HSP70/HSP90-Organizing protein contributes to gastric cancer progression in an autocrine fashion and predicts poor survival in gastric cancer. Cell Physiol Biochem. 47:879–892. 2018. View Article : Google Scholar : PubMed/NCBI

8 

Walsh N, Larkin A, Swan N, Conlon K, Dowling P, McDermott R and Clynes M: RNAi knockdown of Hop (Hsp70/Hsp90 organising protein) decreases invasion via MMP-2 down regulation. Cancer Lett. 306:180–189. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Baindur-Hudson S, Edkins AL and Blatch GL: Hsp70/Hsp90 organising protein (hop): Beyond interactions with chaperones and prion proteins. Subcell Biochem. 78:69–90. 2015. View Article : Google Scholar

10 

Liu B, Ma W, Jha RK and Gurung K: Cancer stem cells in osteosarcoma: Recent progress and perspective. Acta Oncol. 50:1142–1150. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Yang M, Yan M, Zhang R, Li J and Luo Z: Side population cells isolated from human osteosarcoma are enriched with tumor-initiating cells. Cancer Sci. 102:1774–1781. 2011. View Article : Google Scholar : PubMed/NCBI

12 

Gibbs CP, Kukekov VG, Reith JD, Tchigrinova O, Suslov ON, Scott EW, Ghivizzani SC, Ignatova TN and Steindler DA: Stem-like cells in bone sarcomas: Implications for tumorigenesis. Neoplasia. 7:967–976. 2005. View Article : Google Scholar : PubMed/NCBI

13 

Koka P, Mundre RS, Rangarajan R, Chandramohan Y, Subramanian RK and Dhanasekaran A: Uncoupling Warburg effect and stemness in CD133+ve cancer stem cells from Saos-2 (osteosarcoma) cell line under hypoxia. Mol Biol Rep. 45:1653–1662. 2018. View Article : Google Scholar : PubMed/NCBI

14 

Ni M, Xiong M, Zhang X, Cai G, Chen H, Zeng Q and Yu Z: Poly(lactic-co-glycolic acid) nanoparticles conjugated with CD133 aptamers for targeted salinomycin delivery to CD133+ osteosarcoma cancer stem cells. Int J Nanomedicine. 10:2537–2554. 2015. View Article : Google Scholar :

15 

Yang J, Guo W, Wang L, Yu L, Mei H, Fang S, Ji P, Liu Y, Liu G and Song Q: Cisplatin-resistant osteosarcoma cells possess cancer stem cell properties in a mouse model. Oncol Lett. 12:2599–2605. 2016. View Article : Google Scholar : PubMed/NCBI

16 

Brown HK, Tellez-Gabriel M and Heymann D: Cancer stem cells in osteosarcoma. Cancer Lett. 386:189–195. 2017. View Article : Google Scholar

17 

Li K, Li X, Tian J, Wang H, Pan J and Li J: Downregulation of DNA-PKcs suppresses P-gp expression via inhibition of the Akt/NF-κB pathway in CD133-positive osteosarcoma MG-63 cells. Oncol Rep. 36:1973–1980. 2016. View Article : Google Scholar : PubMed/NCBI

18 

Gong C, Liao H, Guo F, Qin L and Qi J: Implication of expression of Nanog in prostate cancer cells and their stem cells. J Huazhong Univ Sci Technolog Med Sci. 32:242–246. 2012. View Article : Google Scholar : PubMed/NCBI

19 

Gong C, Liao H, Wang J, Lin Y, Qi J, Qin L, Tian LQ and Guo FJ: LY294002 induces G0/G1 cell cycle arrest and apoptosis of cancer stem-like cells from human osteosarcoma via down-regulation of PI3K activity. Asian Pac J Cancer Prev. 13:3103–3107. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar

21 

Li J, Sun X, Wang Z, Chen L, Li D, Zhou J and Liu M: Regulation of vascular endothelial cell polarization and migration by Hsp70/Hsp90-organizing protein. PLoS One. 7:e363892012. View Article : Google Scholar : PubMed/NCBI

22 

Abarrategi A, Tornin J, Martinez-Cruzado L, Hamilton A, Martinez-Campos E, Rodrigo JP, González MV, Baldini N, Garcia-Castro J and Rodriguez R: Osteosarcoma: Cells-of-Origin, cancer stem cells, and targeted therapies. Stem Cells Int. 2016:36317642016. View Article : Google Scholar : PubMed/NCBI

23 

Qi XT, Li YL, Zhang YQ, Xu T, Lu B, Fang L, Gao JQ, Yu LS, Zhu DF, Yang B, et al: KLF4 functions as an oncogene in promoting cancer stem cell-like characteristics in osteosarcoma cells. Acta Pharmacol Sin. 40:546–555. 2019. View Article : Google Scholar :

24 

Chang Y, Zhao Y, Zhan H, Wei X, Liu T and Zheng B: Bufalin inhibits the differentiation and proliferation of human osteosarcoma cell line hMG63-derived cancer stem cells. Tumour Biol. 35:1075–1082. 2014. View Article : Google Scholar

25 

Chen F, Zeng Y, Qi X, Chen Y, Ge Z, Jiang Z, Zhang X, Dong Y, Chen H and Yu Z: Targeted salinomycin delivery with EGFR and CD133 aptamers based dual-ligand lipid-polymer nanoparticles to both osteosarcoma cells and cancer stem cells. Nanomedicine. 14:2115–2127. 2018. View Article : Google Scholar : PubMed/NCBI

26 

Xu YW, Liu CT, Huang XY, Huang LS, Luo YH, Hong CQ, Guo HP, Xu LY, Peng YH and Li EM: Serum Autoantibodies against STIP1 as a potential biomarker in the diagnosis of esophageal squamous cell carcinoma. Dis Markers. 2017:53840912017. View Article : Google Scholar : PubMed/NCBI

27 

Huang L, Zhai E, Cai S, Lin Y, Liao J, Jin H, Peng S, Xu L, Chen M and Zeng Z: Stress-inducible Protein-1 promotes metastasis of gastric cancer via Wnt/β-catenin signaling pathway. J Exp Clin Cancer Res. 37:62018. View Article : Google Scholar

28 

Iglesia RP, Prado MB, Cruz L, Martins VR, Santos TG and Lopes MH: Engagement of cellular prion protein with the co-chaperone Hsp70/90 organizing protein regulates the proliferation of glioblastoma stem-like cells. Stem Cell Res Ther. 8:762017. View Article : Google Scholar : PubMed/NCBI

29 

Wang HS, Tsai CL, Chang PY, Chao A, Wu RC, Chen SH, Wang CJ, Yen CF, Lee YS and Wang TH: Positive associations between upregulated levels of stress-induced phosphoprotein 1 and matrix metalloproteinase-9 in endometriosis/adenomyosis. PLoS One. 13:e1905732018.

30 

Erlich RB, Kahn SA, Lima FR, Muras AG, Martins RA, Linden R, Chiarini LB, Martins VR and Moura Neto V: STI1 promotes glioma proliferation through MAPK and PI3K path-ways. Glia. 55:1690–1698. 2007. View Article : Google Scholar : PubMed/NCBI

31 

Tsai CL, Chao A, Jung SM, Tsai CN, Lin CY, Chen SH, Sue SC, Wang TH, Wang HS and Lai CH: Stress-induced phospho-protein-1 maintains the stability of JAK2 in cancer cells. Oncotarget. 7:50548–50563. 2016. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Wang JH, Gong C, Guo FJ, Zhou X, Zhang MS, Qiu H, Chao TF, Liu Y, Qin L, Xiong HH, Xiong HH, et al: Knockdown of STIP1 inhibits the invasion of CD133‑positive cancer stem‑like cells of the osteosarcoma MG63 cell line via the PI3K/Akt and ERK1/2 pathways. Int J Mol Med 46: 2251-2259, 2020.
APA
Wang, J., Gong, C., Guo, F., Zhou, X., Zhang, M., Qiu, H. ... Xiong, H. (2020). Knockdown of STIP1 inhibits the invasion of CD133‑positive cancer stem‑like cells of the osteosarcoma MG63 cell line via the PI3K/Akt and ERK1/2 pathways. International Journal of Molecular Medicine, 46, 2251-2259. https://doi.org/10.3892/ijmm.2020.4764
MLA
Wang, J., Gong, C., Guo, F., Zhou, X., Zhang, M., Qiu, H., Chao, T., Liu, Y., Qin, L., Xiong, H."Knockdown of STIP1 inhibits the invasion of CD133‑positive cancer stem‑like cells of the osteosarcoma MG63 cell line via the PI3K/Akt and ERK1/2 pathways". International Journal of Molecular Medicine 46.6 (2020): 2251-2259.
Chicago
Wang, J., Gong, C., Guo, F., Zhou, X., Zhang, M., Qiu, H., Chao, T., Liu, Y., Qin, L., Xiong, H."Knockdown of STIP1 inhibits the invasion of CD133‑positive cancer stem‑like cells of the osteosarcoma MG63 cell line via the PI3K/Akt and ERK1/2 pathways". International Journal of Molecular Medicine 46, no. 6 (2020): 2251-2259. https://doi.org/10.3892/ijmm.2020.4764
Copy and paste a formatted citation
x
Spandidos Publications style
Wang JH, Gong C, Guo FJ, Zhou X, Zhang MS, Qiu H, Chao TF, Liu Y, Qin L, Xiong HH, Xiong HH, et al: Knockdown of STIP1 inhibits the invasion of CD133‑positive cancer stem‑like cells of the osteosarcoma MG63 cell line via the PI3K/Akt and ERK1/2 pathways. Int J Mol Med 46: 2251-2259, 2020.
APA
Wang, J., Gong, C., Guo, F., Zhou, X., Zhang, M., Qiu, H. ... Xiong, H. (2020). Knockdown of STIP1 inhibits the invasion of CD133‑positive cancer stem‑like cells of the osteosarcoma MG63 cell line via the PI3K/Akt and ERK1/2 pathways. International Journal of Molecular Medicine, 46, 2251-2259. https://doi.org/10.3892/ijmm.2020.4764
MLA
Wang, J., Gong, C., Guo, F., Zhou, X., Zhang, M., Qiu, H., Chao, T., Liu, Y., Qin, L., Xiong, H."Knockdown of STIP1 inhibits the invasion of CD133‑positive cancer stem‑like cells of the osteosarcoma MG63 cell line via the PI3K/Akt and ERK1/2 pathways". International Journal of Molecular Medicine 46.6 (2020): 2251-2259.
Chicago
Wang, J., Gong, C., Guo, F., Zhou, X., Zhang, M., Qiu, H., Chao, T., Liu, Y., Qin, L., Xiong, H."Knockdown of STIP1 inhibits the invasion of CD133‑positive cancer stem‑like cells of the osteosarcoma MG63 cell line via the PI3K/Akt and ERK1/2 pathways". International Journal of Molecular Medicine 46, no. 6 (2020): 2251-2259. https://doi.org/10.3892/ijmm.2020.4764
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