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2015 ; 35
(19
): 3423-35
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CRB3A Controls the Morphology and Cohesion of Cancer Cells through
Ehm2/p114RhoGEF-Dependent Signaling
#MMPMID26217016
Loie E
; Charrier LE
; Sollier K
; Masson JY
; Laprise P
Mol Cell Biol
2015[Oct]; 35
(19
): 3423-35
PMID26217016
show ga
The transmembrane protein CRB3A controls epithelial cell polarization.
Elucidating the molecular mechanisms of CRB3A function is essential as this
protein prevents the epithelial-to-mesenchymal transition (EMT), which
contributes to tumor progression. To investigate the functional impact of altered
CRB3A expression in cancer cells, we expressed CRB3A in HeLa cells, which are
devoid of endogenous CRB3A. While control HeLa cells display a patchy F-actin
distribution, CRB3A-expressing cells form a circumferential actomyosin belt. This
reorganization of the cytoskeleton is accompanied by a transition from an ameboid
cell shape to an epithelial-cell-like morphology. In addition, CRB3A increases
the cohesion of HeLa cells. To perform these functions, CRB3A recruits p114RhoGEF
and its activator Ehm2 to the cell periphery using both functional motifs of its
cytoplasmic tail and increases RhoA activation levels. ROCK1 and ROCK2 (ROCK1/2),
which are critical effectors of RhoA, are also essential to modulate the
cytoskeleton and cell shape downstream of CRB3A. Overall, our study highlights
novel roles for CRB3A and deciphers the signaling pathway conferring to CRB3A the
ability to fulfill these functions. Thereby, our data will facilitate further
investigation of CRB3A functions and increase our understanding of the cellular
defects associated with the loss of CRB3A expression in cancer cells.