TMEM116 is required for lung cancer cell motility and metastasis through PDK1 signaling pathway

Abstract

AbstractTransmembrane protein (TMEM) is a family of protein that spans cytoplasmic membranes and allows cell–cell and cell–environment communication. Dysregulation of TMEMs has been observed in multiple cancers. However, little is known about TMEM116 in cancer development. In this study, we demonstrate that TMEM116 is highly expressed in non-small-cell lung cancer (NSCLC) tissues and cell lines. Inactivation of TMEM116 reduced cell proliferation, migration and invasiveness of human cancer cells and suppressed A549 induced tumor metastasis in mouse lungs. In addition, TMEM116 deficiency inhibited PDK1-AKT-FOXO3A signaling pathway, resulting in accumulation of TAp63, while activation of PDK1 largely reversed the TMEM116 deficiency induced defects in cancer cell motility, migration and invasive. Together, these results demonstrate that TMEM116 is a critical integrator of oncogenic signaling in cancer metastasis.