Epithelial Membrane Protein 2 and β1 integrin signaling regulate APC-mediated processes

Alyssa C. Lesko, Jenifer Prosperi

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Adenomatous Polyposis Coli (APC) plays a critical role in cell motility, maintenance of apical-basal polarity, and epithelial morphogenesis. We previously demonstrated that APC loss in Madin Darby Canine Kidney (MDCK) cells increases cyst size and inverts polarity independent of Wnt signaling, and upregulates the tetraspan protein, Epithelial Membrane Protein 2 (EMP2). Herein, we show that APC loss increases β1 integrin expression and migration of MDCK cells. Through 3D in vitro model systems and 2D migration analysis, we have depicted the molecular mechanism(s) by which APC influences polarity and cell motility. EMP2 knockdown in APC shRNA cells revealed that APC regulates apical-basal polarity and cyst size through EMP2. Chemical inhibition of β1 integrin and its signaling components, FAK and Src, indicated that APC controls cyst size and migration, but not polarity, through β1 integrin and its downstream targets. Combined, the current studies have identified two distinct and novel mechanisms required for APC to regulate polarity, cyst size, and cell migration independent of Wnt signaling.

Original languageEnglish (US)
Pages (from-to)190-198
Number of pages9
JournalExperimental Cell Research
Volume350
Issue number1
DOIs
StatePublished - Jan 1 2017

Fingerprint

Adenomatous Polyposis Coli
Integrins
Cysts
Cell Movement
Membrane Proteins
Madin Darby Canine Kidney Cells
epithelial membrane protein-1
Morphogenesis
Small Interfering RNA
Up-Regulation
Maintenance

Keywords

  • 3D morphology
  • APC
  • Apical-basal polarity
  • EMP2
  • Migration
  • β1 integrin

ASJC Scopus subject areas

  • Cell Biology

Cite this

Epithelial Membrane Protein 2 and β1 integrin signaling regulate APC-mediated processes. / Lesko, Alyssa C.; Prosperi, Jenifer.

In: Experimental Cell Research, Vol. 350, No. 1, 01.01.2017, p. 190-198.

Research output: Contribution to journalArticle

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