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 language | English (US) |
|---|---|
| Pages (from-to) | 190-198 |
| Number of pages | 9 |
| Journal | Experimental Cell Research |
| Volume | 350 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2017 |
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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 journal › Article
}
TY - JOUR
T1 - Epithelial Membrane Protein 2 and β1 integrin signaling regulate APC-mediated processes
AU - Lesko, Alyssa C.
AU - Prosperi, Jenifer
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
AB - 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.
KW - 3D morphology
KW - APC
KW - Apical-basal polarity
KW - EMP2
KW - Migration
KW - β1 integrin
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UR - http://www.scopus.com/inward/citedby.url?scp=85006976130&partnerID=8YFLogxK
U2 - 10.1016/j.yexcr.2016.11.021
DO - 10.1016/j.yexcr.2016.11.021
M3 - Article
C2 - 27890644
AN - SCOPUS:85006976130
VL - 350
SP - 190
EP - 198
JO - Experimental Cell Research
JF - Experimental Cell Research
SN - 0014-4827
IS - 1
ER -