Abstract 4535: The mTOR complex 2 promotes glioblastoma migration via the interactions with multiple actin-binding and microtubule-associated proteins

The mechanistic target of rapamycin complex 2 (mTORC2) is one of the two multiprotein complexes in the mTOR signaling pathway. It regulates several cellular activities such as cell survival, lipid metabolism, DNA damage control, and cell motility. The mTORC2 has been reported to be involved in the promotion of metabolic reprogramming, cancer migration, and cancer invasiveness in glioblastoma. However, underlying mechanisms and roles of this particular complex in glioblastoma migration has not been completely elucidated. Previously, we characterized the mTORC2-associated interactome by affinity purification-mass spectrometry (AP-MS) technique, identifying new RICTOR-interacting partners. In addition, we also investigated the localization of RICTOR under different culture conditions and found that it correlates with migration ability of the cancer cells. When mTORC2 activity is high resulting in increased migration, RICTOR tends to localize around the cell membrane. In this work, we further determined crucial players that interact with mTORC2 to control actin cytoskeleton and microtubule dynamics to promote migration. The results from quantitative proteomic analysis of mTORC2-associated interactome suggested that the amount of certain actin-binding proteins and microtubule-associated proteins significantly changed depending on mTORC2 activity level including Gelsolin, Myosin-9, Plectin, and MAP1B. When mTORC2 signaling was inhibited resulting in reduced migration, these proteins were found to be less interacting with mTORC2. Moreover, the results also indicated that active mTORC2 links both actin cytoskeleton and microtubules together to promote migration in glioblastoma cells. Depletion of RICTOR and inhibition of mTORC2 disrupted the connection between microtubules and cell membrane. Taken together, this work provided a plausible mechanism underlying the regulation of enhanced migration in brain cancer cells. Citation Format: Naphat Chantaravisoot, Piriya Wongkongkathep, Narawit Pacharakullanon, Fuyuhiko Tamanoi, Joseph A. Loo, Trairak Pisitkun. The mTOR complex 2 promotes glioblastoma migration via the interactions with multiple actin-binding and microtubule-associated proteins [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4535.