title: The extracellular matrix microtopography drives critical changes in cellular motility and Rho A activity in colon cancer cells.
abstract: We have shown that the microtopography (mT) underlying colon cancer changes as a tumor de-differentiates. We distinguish the well-differentiated mT based on the increasing number of "pits" and poorly differentiated mT on the basis of increasing number of "posts." We investigated Rho A as a mechanosensing protein using mT features derived from those observed in the ECM of colon cancer. We evaluated Rho A activity in less-tumorogenic (Caco-2 E) and more tumorigenic (SW620) colon cancer cell-lines on microfabricated pits and posts at 2.5 mum diameter and 200 nm depth/height. In Caco-2 E cells, we observed a decrease in Rho A activity as well as in the ratio of G/F actin on surfaces with either pits or posts but despite this low activity, knockdown of Rho A led to a significant decrease in confined motility suggesting that while Rho A activity is reduced on these surfaces it still plays an important role in controlling cellular response to barriers. In SW620 cells, we observed that Rho A activity was greatest in cells plated on a post microtopography which led to increased cell motility, and an increase in actin cytoskeletal turnover.
authors.affiliation: University of Illinois at Chicago, Chicago, IL USA. sarahg@uic.edu.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Rapier
authors.forename: Jameela
authors.initials: J
authors.lastname: Huq
authors.forename: Ramana
authors.initials: R
authors.lastname: Vishnubhotla
authors.forename: Marinka
authors.initials: M
authors.lastname: Bulic
authors.forename: Cecile M
authors.initials: CM
authors.lastname: Perrault
authors.forename: Vitali
authors.initials: V
authors.lastname: Metlushko
authors.forename: Michael
authors.initials: M
authors.lastname: Cho
authors.forename: Roger Tran Son
authors.initials: RT
authors.lastname: Tay
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Glover