The extracellular matrix microtopography drives critical changes in cellular motility and Rho A activity in colon cancer cells

• Published in: Cancer cell international 2010-07, Vol.10 (1), p.24-24, Article 24
• Main Authors: Rapier, Rebecca, Huq, Jameela, Vishnubhotla, Ramana, Bulic, Marinka, Perrault, Cecile M, Metlushko, Vitali, Cho, Michael, Tay, Roger Tran Son, Glover, Sarah C
• Format: Article
• Language: English
• Subjects: Primary Research
• ISSN: 1475-2867; 1475-2867
• DOI: 10.1186/1475-2867-10-24

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.