Title: Integrin trafficking and cancer invasion
Date/venue: Thursday November 24th 13.00 in the Auditorium in the research building at the Radium Hospital
Integrins are cell adhesion receptors involved in mediating the invasive migration, growth and metastasis of cancer cells. We have established that Rab-regulated integrin trafficking contributes to cell migration, and have now obtained detailed descriptions of the molecular machinery of integrin transport and determined how this contributes to invasive migration of cancer cells through three-dimensional matrices. For instance, we have shown that the Rab11 family member, Rab25, can promote invasion by associating with and controlling the trafficking and spatial restriction of á5â1 integrin. More recently, we reported that mutant forms of p53 drive cancer invasion by activating the Rab11 effector, Rab-coupling protein (RCP) to coordinate á5â1 integrin and EGFR1 trafficking. In this talk, I will present data describing two novel aspects of integrin trafficking in cancer cell migration. Firstly, I will describe how the Chloride Intracellular Channel Protein 3 (CLIC3) acts to recycle active integrins that have been targetted to late endosomes/lysosomes by the action of Rab25, and present clinical data indicating that this event likely contributes to the invasion and metastasis of pancreatic ductal adenocarcinoma in vivo. Secondly, I will present the advances that we have made in looking at mutant p53s control of RCP function, in particular the role of that microRNAs and phosphatidic acid signalling play in this process.
Refreshments and discussions in the lobby after the talk.