The Vacuole Membrane Protein 1 - VMP1 - is a novel target gene target gene required for HIF-1-induced autophagy in colon cancer cell and prevents cell death after photodynamic therapy.

CATRINACIO, C.; VACCARO, M. I.; ALEJANDRO JAVIER ROPOLO

Buenos Aires

Congreso; III International Congress in Translational Medicine; 2016

International Master/PhD Program in Biomedical Sciences (IMBS). Facultad de Farmacia y Bioquímica y Facultad de Medicina, Universidad de Buenos Aires.

Hypoxia is a common feature in solid tumor and leads to chemo/radio resistance. Recently it has been shown that in response to hypoxia, cell can induce HIF-1α-mediated autophagy to survive in its hostile microenvironment. Moreover, hypoxia and autophagy have been implicated in resistance to antitumor photodynamic therapy (PDT). However, the interplay between HIF-1α and autophagy in PDT context has not been studied yet. Here we evaluate the role of HIF-1α and autophagy as well as the underlying mechanism in the PDT resistance of colon cancer cells. Our study demonstrates that under hypoxia mimic, HIF-1α significantly increases VMP1-related autophagy through binding to hypoxia responsive elements in VMP1 promoter. We show that HIF-1α-induced autophagy, increases cell survival of CaCo2 and Sw480 cells after PDT. Moreover, PDT is able to trigger HIF-1α/VMP1-induced autophagy and the inhibition of autophagy with 3-Ma, Chloroquine, wortmannin or shRNA targeted to VMP1 decreases cell survival after phototherapy. In conclusion, PDT induces autophagy as a survival mechanism and the induction of the novel HIF-1α/VMP1-autophagic pathway may explain PDT resistance in colon cancer cells.