Role of mTOR Signaling in Tumor Cell Motility, Invasion and Metastasis

Tumor cell migration and invasion play fundamental roles in cancer metastasis. The mammalian target of rapamycin (mTOR), a highly conserved and ubiquitously expressed serine/threonine (Ser/Thr) kinase, is a central regulator of cell growth, proliferation, differentiation and survival. Recent studies have demonstrated that mTOR also plays a critical role in the regulation of tumor cell motility, invasion and cancer metastasis. Current knowledge indicates that mTOR functions as two distinct multiprotein complexes, mTORC1 and mTORC2. mTORC1 phosphorylates p70 S6 kinase (S6K1) and eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1), and regulates cell growth, proliferation, survival and motility. mTORC2 phosphorylates Akt, protein kinase C α (PKCα) and the focal adhesion proteins, and controls the activities of the small GTPases (RhoA, Cdc42 and Rac1), and regulates cell survival and the actin cytoskeleton. Here we briefly review current knowledge of mTOR complexes and the role of mTOR signaling in tumor cell migration and invasion. We also discuss recent findings about the mechanism by which rapamycin inhibits cell migration, invasion and cancer metastasis.

Keywords: Akt, Cell motility, Focal adhesion proteins, GTPases, Invasion, Metastasis, mTOR, mTORC1, mTORC2, Rapamycin, S6K1, 4E-BP1.