| First Author | Yoon SO | Year | 2017 |
| Journal | Mol Cell | Volume | 67 |
| Issue | 3 | Pages | 512-527.e4 |
| PubMed ID | 28757207 | Mgi Jnum | J:253560 |
| Mgi Id | MGI:6106666 | Doi | 10.1016/j.molcel.2017.06.033 |
| Citation | Yoon SO, et al. (2017) Focal Adhesion- and IGF1R-Dependent Survival and Migratory Pathways Mediate Tumor Resistance to mTORC1/2 Inhibition. Mol Cell 67(3):512-527.e4 |
| abstractText | Aberrant signaling by the mammalian target of rapamycin (mTOR) contributes to the devastating features of cancer cells. Thus, mTOR is a critical therapeutic target and catalytic inhibitors are being investigated as anti-cancer drugs. Although mTOR inhibitors initially block cell proliferation, cell viability and migration in some cancer cells are quickly restored. Despite sustained inhibition of mTORC1/2 signaling, Akt, a kinase regulating cell survival and migration, regains phosphorylation at its regulatory sites. Mechanistically, mTORC1/2 inhibition promotes reorganization of integrin/focal adhesion kinase-mediated adhesomes, induction of IGFR/IR-dependent PI3K activation, and Akt phosphorylation via an integrin/FAK/IGFR-dependent process. This resistance mechanism contributes to xenograft tumor cell growth, which is prevented with mTOR plus IGFR inhibitors, supporting this combination as a therapeutic approach for cancers. |
