TY - JOUR
T1 - Novel regulation of integrin trafficking by rab11-FIP5 in aggressive prostate cancer
AU - Das, Lipsa
AU - Gard, Jaime M.C.
AU - Prekeris, Rytis
AU - Nagle, Raymond B.
AU - Morrissey, Colm
AU - Knudsen, Beatrice S.
AU - Miranti, Cindy K.
AU - Cress, Anne E.
N1 - Funding Information:
Rab11-FIP5-GFP–mutant cDNA constructs were a kind gift from Dr. Rytis Prekeris. We thank Lucas Heppner who analyzed expression of b4 integrin in PC3N cells. We appreciate the support from Dr. Greg Rogers and his lab members for use of the Deltavision Core deconvolution microscope. We acknowledge the institutional support from Cedars Sinai Medical Center, Los Angeles, CA for IHC analysis by their Biobank and Translational Research Core. We thank the patients and their families who were willing to participate in the Prostate Cancer Donor Program. Research at Cedars Sinai Medical Center was supported by Pacific Northwest Prostate Cancer SPORE (P50CA97186), the PO1 NIH grant (PO1CA085859), and the Richard M. LUCAS Foundation. Research at the University of Colorado was supported in part by NIH-NIDDKR01-DK064380 (to R. Prekeris), research at the University of Arizona was supported in part by NIH-NCIRO1CA159406 (to J.M.C. Gard, A.E. Cress), NIH-NCIRO1CA154835 (to C. Miranti), P30CA23074, and The Tim and Diane Bowden Cancer Biology Fellowship Award (to L. Das).
Publisher Copyright:
© 2018 American Association for Cancer Research.
PY - 2018/8
Y1 - 2018/8
N2 - The laminin-binding integrins, a3b1 and a6b1, are needed for tumor metastasis and their surface expression is regulated by endocytic recycling. b1 integrins share the Rab11 recycling machinery, but the trafficking of a3b1 and a6b1 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 a6b1 recycling, without affecting the other laminin-binding integrin (i.e., a3b1) or unrelated membrane receptors like CD44, transferrin receptor, or E-cadherin. Depletion of Rab11-FIP5 resulted in the intracellular accumulation of a6b1 in the Rab11 recycling compartment, loss of cell migration on laminin, and an unexpected loss of a6b1 recycling in cell–cell locations. Taken together, these data demonstrate that a6b1 is distinct from a3b1 via Rab11-FIP5 recycling and recycles in an unexpected cell–cell location. Implications: Rab11-FIP5–dependent a6b1 integrin recycling may be selectively targeted to limit migration of prostate cancer cells into laminin-rich tissues.
AB - The laminin-binding integrins, a3b1 and a6b1, are needed for tumor metastasis and their surface expression is regulated by endocytic recycling. b1 integrins share the Rab11 recycling machinery, but the trafficking of a3b1 and a6b1 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 a6b1 recycling, without affecting the other laminin-binding integrin (i.e., a3b1) or unrelated membrane receptors like CD44, transferrin receptor, or E-cadherin. Depletion of Rab11-FIP5 resulted in the intracellular accumulation of a6b1 in the Rab11 recycling compartment, loss of cell migration on laminin, and an unexpected loss of a6b1 recycling in cell–cell locations. Taken together, these data demonstrate that a6b1 is distinct from a3b1 via Rab11-FIP5 recycling and recycles in an unexpected cell–cell location. Implications: Rab11-FIP5–dependent a6b1 integrin recycling may be selectively targeted to limit migration of prostate cancer cells into laminin-rich tissues.
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U2 - 10.1158/1541-7786.MCR-17-0589
DO - 10.1158/1541-7786.MCR-17-0589
M3 - Article
C2 - 29759989
AN - SCOPUS:85050972013
VL - 16
SP - 1319
EP - 1331
JO - Cell Growth and Differentiation
JF - Cell Growth and Differentiation
SN - 1541-7786
IS - 8
ER -