Role of mTOR Signaling in Tumor Cell Motility, Invasion and Metastasis
Pp. 207-244 (38)
Hongyu Zhou and Shile Huang
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.
Akt, Cell motility, Focal adhesion proteins, GTPases, Invasion,
Metastasis, mTOR, mTORC1, mTORC2, Rapamycin, S6K1, 4E-BP1.
Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130-3932, USA.