Novel regulation of integrin trafficking by rab11-FIP5 in aggressive prostate cancer

Lipsa Das, Jaime M.C. Gard, Rytis Prekeris, Raymond B Nagle, Colm Morrissey, Beatrice S. Knudsen, Cindy K. Miranti, Anne E Cress

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1319-1331
Number of pages13
JournalMolecular Cancer Research
Volume16
Issue number8
DOIs
StatePublished - Aug 1 2018

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Recycling
Integrins
Prostatic Neoplasms
Laminin
Proteins
Transferrin Receptors
Membranes
Cadherins
Cell Movement
Neoplasms
Neoplasm Metastasis

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

Cite this

Novel regulation of integrin trafficking by rab11-FIP5 in aggressive prostate cancer. / Das, Lipsa; Gard, Jaime M.C.; Prekeris, Rytis; Nagle, Raymond B; Morrissey, Colm; Knudsen, Beatrice S.; Miranti, Cindy K.; Cress, Anne E.

In: Molecular Cancer Research, Vol. 16, No. 8, 01.08.2018, p. 1319-1331.

Research output: Contribution to journalArticle

Das, Lipsa ; Gard, Jaime M.C. ; Prekeris, Rytis ; Nagle, Raymond B ; Morrissey, Colm ; Knudsen, Beatrice S. ; Miranti, Cindy K. ; Cress, Anne E. / Novel regulation of integrin trafficking by rab11-FIP5 in aggressive prostate cancer. In: Molecular Cancer Research. 2018 ; Vol. 16, No. 8. pp. 1319-1331.
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