%0 Journal Article
%T Hakai reduces cell-substratum adhesion and increases epithelial cell invasion
%A Teresa Rodr¨ªguez-Rigueiro
%A Manuel Valladares-Ayerbes
%A Mar Haz-Conde
%A Luis A Aparicio
%A Ang¨¦lica Figueroa
%J BMC Cancer
%D 2011
%I BioMed Central
%R 10.1186/1471-2407-11-474
%X Parental MDCK cells and MDCK cells stably overexpressing Hakai were used to analyse cell-substratum adhesion and invasion capabilities. Western blot and immunofluoresecence analyses were performed to assess the roles of Paxillin, FAK and Vinculin in cell-substratum adhesion. The role of the proteasome in controlling cell-substratum adhesion was studied using two proteasome inhibitors, lactacystin and MG132. To study the molecular mechanisms controlling Paxillin expression, MDCK cells expressing E-cadherin shRNA in a tetracycline-inducible manner was employed.Here, we present evidence that implicate Hakai in reducing cell-substratum adhesion and increasing epithelial cell invasion, two hallmark features of cancer progression and metastasis. Paxillin, an important protein component of the cell-matrix adhesion, was completely absent from focal adhesions and focal contacts in Hakai-overexpressing MDCK cells. The expression of Paxillin was found to be regulated by a proteasome-independent mechanism, possibly due to the decreased abundance of E-cadherin.Taken together, these results suggest that Hakai may be involved in two hallmark aspects of tumour progression, the lowering cell-substratum adhesion and the enhancement of cell invasion.The most frequent types of tumours are carcinomas, which develop through the transformation of epithelial cells. Epithelial cells are polarized and are often connected with each other via cell-cell adhesions to form structured cells sheets. The formation of these tight and compact cell-cell adhesions restricts cell movement within the epithelium. Epithelial cells are also attached to an extracellular matrix substratum which is essential for their differentiation and polarization [1]. During transformation, epithelial cells start to proliferate, acquire the ability to migrate, and lose both the intercellular adhesion, mediated by cadherins at adherens junctions, and the interactions with the extracellular matrix. All of these characteristic
%U http://www.biomedcentral.com/1471-2407/11/474