Hic-5 expression is a major indicator of cancer cell morphology, migration, and plasticity in three-dimensional matrices

Molecular Biology of the Cell
Anushree C GulvadyChristopher E Turner

Abstract

The focal adhesion proteins Hic-5 and paxillin have been previously identified as key regulators of MDA-MB-231 breast cancer cell migration and morphologic mesenchymal-amoeboid plasticity in three-dimensional (3D) extracellular matrices (ECMs). However, their respective roles in other cancer cell types have not been evaluated. Herein, utilizing 3D cell-derived matrices and fibronectin-coated one-dimensional substrates, we show that across a variety of cancer cell lines, the level of Hic-5 expression serves as the major indicator of the cells primary morphology, plasticity, and in vitro invasiveness. Domain mapping studies reveal sites critical to the functions of both Hic-5 and paxillin in regulating phenotype, while ectopic expression of Hic-5 in cell lines with low endogenous levels of the protein is sufficient to induce a Rac1-dependent mesenchymal phenotype and, in turn, increase amoeboid-mesenchymal plasticity and invasion. We show that the activity of vinculin, when coupled to the expression of Hic-5 is required for the mesenchymal morphology in the 3D ECM. Taken together, our results identify Hic-5 as a critical modulator of tumor cell phenotype that could be utilized in predicting tumor cell migratory and invasive behav...Continue Reading

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Citations

Mar 21, 2019·Molecular Biology of the Cell·Anushree C GulvadyChristopher E Turner
Oct 5, 2019·Nature Reviews. Molecular Cell Biology·Kenneth M Yamada, Michael Sixt
Oct 24, 2019·Molecular Biology of the Cell·Rishel B VohnoutkaChristopher E Turner
Feb 29, 2020·Ci Ji Yi Xue Za Zhi = Tzu-chi Medical Journal·Wen-Sheng Wu
Mar 12, 2021·Cell Communication and Signaling : CCS·Susan E LeggettIan Y Wong
Jul 19, 2021·Free Radical Biology & Medicine·Joyce BagyiDana R Crawford

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Methods Mentioned

BETA
GTPase
proximity ligation assay
transfection
confocal microscopy

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