The role of autophagy in cancer cell motility (360G-Wellcome-205889_Z_17_Z)

This project will investigate the role of autophagy in cell motility taking advantage of novel prostate cancer cell lines that mimic stages of disease progression (including EMT and metastasis) available through my collaborators at NTU. In particular it will address the role of the actin nucleator JMY, a p53 co-factor that impacts of autophagosome formation, cell motility and survival in autophagy-mediated effects on cell survival and the role of actin nucleation. Specific goals during the duration of the funding: -assess autophagy levels (both basal and induced) in cancer cells lines and correlate with cell motility and invasion (also assessing cell survival and adhesion/motility events, using impedance measurements, to distinguish between effects on proliferation vs motility). -Assess impact of JMY on autophagy-mediated motility (using specific mutants to distinguish autophagosome targeted vs not, and Arp2/3-independent vs dependent actin nucleation. -Assess impact of modulating autophagy levels on cell motility (i.e., through siRNA/CRISPR-Cas9 targetting of JMY and autophagy initiator proteins and small molecule inhibitors of various stages in autophagosome formation).