AbstractEMC6 (endoplasmic reticulum membrane protein complex subunit 6), also known as transmembrane protein 93, is a novel positive autophagy regulator. In this report, we evaluated the anti-tumor activity of EMC6 in glioblastoma cells in vitro and in vivo. Our data show that overexpression of EMC6 in three glioblastoma cell lines (SHG44, U87 and U251) suppresses tumor cell growth by activating autophagy, but fails to induce cell apoptosis. EMC6-mediated autophagy was associated with inactivation of the PIK3CA/AKT/mTOR signaling pathway. Accordingly, EMC6 knockdown in glioblastoma cells had the opposite effect; it promoted cell growth. Overexpression of EMC6 also sensitized glioblastoma cells to the chemotherapy drug, temozolomide, to further suppress tumor growth. Our data indicate that EMC6-induced autophagy may play a positive role in suppressing the development of glioblastoma.