TSSC3 promotes autophagy via inactivating the Src-mediated PI3K/Akt/mTOR pathway to suppress tumorigenesis and metastasis in osteosarcoma, and predicts a favorable prognosis

Abstract

[...]PHLDA1, the homologous gene of TSSC3 has been demonstrated to trigger autophagy [25]. [...]the PI3K/Akt/mTOR signaling pathway, which is a classical pathway that modulates cell proliferation, apoptosis resistance, and tumorigenesis, is reported to be involved in the regulation of autophagy in several human tumors cells [26, 27] and can be activated by the Src-family kinases [28]. Figure S3 a) in osteosarcoma cells [8]. [...]to determine whether TSSC3-induced inhibition of osteosarcoma malignant proliferation was related to autophagy, we applied the CCK-8 assay to detect the cell viability with or without TSSC3-overexpression, with or without autophagy suppression by CQ. Figure S4d and Fig. 4e). [...]all of the vitro and in vivo results indicated that TSSC3-induced autophagy plays a crucial role in TSSC3-mediated tumorigenesis in osteosarcoma cells. The epithelial-mesenchymal transition (EMT) is a metastatic behavior of cancer cells [38]. [...]the impairment of MTF and SaOS2 cell migration and invasion might be caused by inhibition of the EMT, dependent on TSSC3 overexpression-induced autophagy.