Novel Regulation of Integrin Trafficking by Rab11-FIP5 in Aggressive Prostate Cancer.

ABSTRACT: The laminin-binding integrins, ?3?1 and ?6?1, are needed for tumor metastasis and their surface expression is regulated by endocytic recycling. ?1 integrins share the Rab11 recycling machinery, but the trafficking of ?3?1 and ?6?1 are distinct by an unknown mechanism. Using a mouse PDX tumor model containing human metastatic prostate cancer, Rab11 family interacting protein 5 (Rab11-FIP5) was identified as a lead candidate for ?6?1 trafficking. Rab11-FIP5 and its membrane-binding domain were required for ?6?1 recycling, without affecting the other laminin-binding integrin (i.e., ?3?1) or unrelated membrane receptors like CD44, transferrin receptor, or E-cadherin. Depletion of Rab11-FIP5 resulted in the intracellular accumulation of ?6?1 in the Rab11 recycling compartment, loss of cell migration on laminin, and an unexpected loss of ?6?1 recycling in cell-cell locations. Taken together, these data demonstrate that ?6?1 is distinct from ?3?1 via Rab11-FIP5 recycling and recycles in an unexpected cell-cell location.Implications: Rab11-FIP5-dependent ?6?1 integrin recycling may be selectively targeted to limit migration of prostate cancer cells into laminin-rich tissues. Mol Cancer Res; 16(8); 1319-31. ©2018 AACR.

SUBMITTER: Das L 

PROVIDER: S-EPMC6369592 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature