Open AccessKnockdown 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
Author(s) -
Jianhua Wang,
Gong Chen,
Fengjin Guo,
Zhijie Xiao,
Mingsheng Zhang,
Hong Qian,
Tengfei Chao,
Yang Liu,
Liang Qin,
Huihua Xiong
Publication year - 2020
Publication title -
international journal of molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.048
H-Index - 90
eISSN - 1791-244X
pISSN - 1107-3756
DOI - 10.3892/ijmm.2020.4764
Subject(s) - osteosarcoma , cancer research , oncogene , protein kinase b , biology , gene knockdown , metastasis , pi3k/akt/mtor pathway , cancer stem cell , cell cycle , cell , cell migration , cancer , stem cell , cell culture , microbiology and biotechnology , signal transduction , genetics
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.