Novel Regulation of Integrin Trafficking by Rab11-FIP5 in Aggressive Prostate Cancer
Gard, Jaime M.C.
Nagle, Raymond B.
Knudsen, Beatrice S.
Miranti, Cindy K.
Cress, Anne E.
AffiliationUniv Arizona, Canc Biol Grad Interdisciplinary Program
Univ Arizona, Canc Ctr
Univ Arizona, Canc Ctr, Cellular & Mol Med
Univ Arizona, Canc Ctr, Mol & Cellular Biol
MetadataShow full item record
PublisherAMER ASSOC CANCER RESEARCH
CitationLipsa Das, Jaime M.C. Gard, Rytis Prekeris, et al. Novel Regulation of Integrin Trafficking by Rab11-FIP5 in Aggressive Prostate Cancer. Mol Cancer Res August 1 2018 (16) (8) 1319-1331; DOI: 10.1158/1541-7786.MCR-17-0589
JournalMOLECULAR CANCER RESEARCH
Rights© 2018 American Association for Cancer Research.
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at email@example.com.
AbstractThe laminin-binding integrins, alpha 3 beta 1 and alpha 6 beta 1, are needed for tumor metastasis and their surface expression is regulated by endocytic recycling. beta 1 integrins share the Rab11 recycling machinery, but the trafficking of alpha 3 beta 1 and alpha 6 beta 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 a6b1 trafficking. Rab11-FIP5 and its membrane-binding domain were required for alpha 6 beta 1 recycling, without affecting the other laminin-binding integrin (i.e., alpha 6 beta 1) or unrelated membrane receptors like CD44, transferrin receptor, or E-cad-herin. Depletion of Rab11-FIP5 resulted in the intracellular accumulation of alpha 6 beta 1 in the Rab11 recycling compartment, loss of cell migration on laminin, and an unexpected loss of alpha 6 beta 1 recycling in cell-cell locations. Taken together, these data demonstrate that alpha 6 beta 1 is distinct from alpha 3 beta 1 via Rab11-FIP5 recycling and recycles in an unexpected cell-cell location.
Note12 month embargo; published online: 14 May 2018
VersionFinal accepted manuscript
SponsorsPacific Northwest Prostate Cancer SPORE [P50CA97186]; PO1 NIH grant [PO1CA085859]; Richard M. LUCAS Foundation; Tim and Diane Bowden Cancer Biology Fellowship Award; NIH [NIDDKR01-DK064380]; [NIH-NCIRO1CA159406]; [NIH-NCIRO1CA154835]; [P30CA23074]
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