Regulation of autophagy by Rab27B in colorectal cancer

Autophagy is a cellular recycling process that can promote tumor growth, anti-tumor immune response, and resistance to therapy in colorectal cancer (CRC). Here, we show that small GTPase Rab27B, a known regulator of vesicle trafficking and extracellular vesicle secretion, to control the autophagy process in CRC. Depletion of Rab27B in CRC cells showed an abnormal accumulation of autophagy vesicles and increased autophagy markers, indicating a defect in autophagy flux. Imaging analysis indicated that autophagy flux is blocked at the autophagosome/lysosome fusion step when Rab27B is lost. Loss of Rab27B significantly impacted CRC cell growth in both in vitro 3D growth and in vivo tumorigenesis studies. Together, these results demonstrate a new role of Rab27B in the autophagy trafficking process in CRC and identify Rab27B as a potential therapeutic target for CRC. Overall design: To investigate the effects of Rab27B silencing in colorectal cancer, Rab27B was deleted by CRISPR/Cas9 in CRC cell line HCT116 Three biological replicates were analyzed for each of 2 genotypes (HCT116 wt and Rab27B KO)