ARHGEF9 regulates melanoma morphogenesis in environments with diverse geometry and elasticity by promoting filopodial-driven adhesion.
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ICR Authors
Authors
Bousgouni, V
Inge, O
Robertson, D
Jones, I
Clatworthy, I
Bakal, C
Inge, O
Robertson, D
Jones, I
Clatworthy, I
Bakal, C
Document Type
Journal Article
Date
2022-08-19
Date Accepted
2022-07-14
Abstract
Rho GTP Exchange Factors (RhoGEFs) and Rho GTPase Activating Proteins (RhoGAPs) are large families of molecules that regulate shape determination in all eukaryotes. In pathologies such as melanoma, RhoGEF and RhoGAP activity underpins the ability of cells to invade tissues of varying elasticity. To identify RhoGEFs and RhoGAPs that regulate melanoma cell shape on soft and/or stiff materials, we performed genetic screens, in tandem with single-cell quantitative morphological analysis. We show that ARHGEF9/Collybistin (Cb) is essential for cell shape determination on both soft and stiff materials, and in cells embedded in 3D soft hydrogel. ARHGEF9 is required for melanoma cells to invade 3D matrices. Depletion of ARHGEF9 results in loss of tension at focal adhesions decreased cell-wide contractility, and the inability to stabilize protrusions. Taken together we show that ARHGEF9 promotes the formation of actin-rich filopodia, which serves to establish and stabilize adhesions and determine melanoma cell shape.
Citation
iScience, 2022, 25 (8), pp. 104795 -
Source Title
iScience
Publisher
CELL PRESS
ISSN
2589-0042
eISSN
2589-0042
2589-0042
2589-0042
Collections
Research Team
Dynamical Cell Systems