A ROLE OF PRL-3 IN AUTOPHAGY AND ITS REGULATION IN HUMAN CANCERS

Abstract

PRL-3 (PTP4A3) IS A PHOSPHATASE THAT PROMOTES MULTIPLE ONCOGENIC PROCESSES. RECENTLY, WE FOUND THE CORRELATION OF PRL-3 AND AUTOPHAGY. AUTOPHAGY IS A ?SELF-EATING? PROCESS WHICH HAS DUAL ROLES IN PROMOTING OR SUPPRESSING TUMOR GROWTH, DEPENDING ON CELLULAR CONTEXT. IN THIS STUDY, I SHOWED PRL-3 OVEREXPRESSION ENHANCES HVPS34-BECLIN-1-DEPENDENT AUTOPHAGOSOME FORMATION, AND ACCELERATES ATG5 DEPENDENT LC3 CONVERSION. PRL-3 OVEREXPRESSION ALSO ACCELERATES THE DEGRADATION OF SQSTM/P62, WHICH IS A KNOWN AUTOPHAGY SUBSTRATE. SURPRISINGLY, PRL-3 ITSELF IS ALSO DEGRADED BY AUTOPHAGY, FORMING A NEGATIVE FEEDBACK LOOP WITH AUTOPHAGY. CLINICALLY, PRL-3 IS DEPENDENT ON AUTOPHAGY ACTIVITY IN PROMOTING OVARIAN CANCER PROGRESSION. IN ADDITION, I SHOWED THAT CONSTITUTIVELY ACTIVATED MUTATION OF KRAS, WHICH IS ESSENTIAL IN THE DEVELOPMENT OF MANY HUMAN CANCERS, SPECIFICALLY UPREGULATED PRL-3 PROTEIN LEVEL. MY STUDY SHOWED NEW MECHANISMS OF PRL-3 REGULATIONS AS WELL AS THE PATHWAYS AFFECTED BY PRL-3, WHI