Osteopontin is Critical for Hyperactive mTOR-Induced Tumorigenesis in Oral Squamous Cell Carcinoma

Mechanistic target of rapamycin (mTOR) plays a critical role in the development of oral squamous cell carcinoma (OSCC), but the underlying mechanisms remain poorly understood. Here we have demonstrated that the expression of osteopontin (OPN) was dramatically up-regulated in OSCC tissues and cell lines. Moreover, reduction of OPN suppressed cell proliferation, colony formation, and in vivo tumorigenic ability of OSCC cell lines Tca8113. In addition, there was a strong positive correlation between mTORC1 activity and OPN expression in OSCC tissues and cell lines. Furthermore, mTOR complex 1 (mTORC1) enhanced OPN expression through up-regulation of ERR alpha. Therefore, OPN is a downstream target of mTORC1 and is crucial for OSCC development. mTORC1, ERR alpha, and OPN may be potential targets for treatment of OSCC with aberrant mTORC1 signaling.