Pharmacological Inhibition of mTORC2 Reduces Migration and Metastasis in Melanoma.
Fiche publication
Date publication
décembre 2020
Journal
International journal of molecular sciences
Auteurs
Membres identifiés du Cancéropôle Est :
Dr VENKATASAMY Aina
Tous les auteurs :
Guenzle J, Akasaka H, Joechle K, Reichardt W, Venkatasamy A, Hoeppner J, Hellerbrand C, Fichtner-Feigl S, Lang SA
Lien Pubmed
Résumé
Despite recent advances in therapy, liver metastasis from melanoma is still associated with poor prognosis. Although targeting the mTOR signaling pathway exerts potent anti-tumor activity, little is known about specific mTORC2 inhibition regarding liver metastasis. Using the novel mTORC2 specific inhibitor JR-AB2-011, we show significantly reduced migration and invasion capacity by impaired activation of MMP2 in melanoma cells. In addition, blockade of mTORC2 induces cell death by non-apoptotic pathways and reduces tumor cell proliferation rate dose-dependently. Furthermore, a significant reduction of liver metastasis was detected in a syngeneic murine metastasis model upon therapy with JR-AB2-011 as determined by in vivo imaging and necropsy. Hence, our study for the first time highlights the impact of the pharmacological blockade of mTORC2 as a potent novel anti-cancer approach for liver metastasis from melanoma.
Mots clés
mTORC2, melanoma, metastasis, migration
Référence
Int J Mol Sci. 2020 Dec 22;22(1):