The Rho GTPase RhoB regulates cadherin expression and epithelial cell-cell interaction.

Francisco M Vega,Anne J Ridley,Nicolas Reymond,Mairian Thomas

doi:10.1186/s12964-015-0085-y

Abstract

BackgroundThe Rho GTPase RhoB has been proposed to be a tumor suppressor in cancer and is downregulated in various tumors including prostate. RhoB has different effects on cell migration depending on the cell type and conditions, but the molecular basis for this variability is unclear. RhoB regulates trafficking of membrane receptors and integrins. We have previously shown that RhoB depletion alters focal adhesion dynamics and reduces surface levels of β1 integrin in PC3 prostate cancer cells, correlating with increased migration speed.ResultsHere we show that RhoB depletion reduces cell-cell adhesion and downregulates E-cadherin levels as well as increasing internalized E-cadherin in DU145 prostate cancer cells. This is accompanied by increased migration speed. RhoB localizes to cell-cell junctions together with E-cadherin in DU145 cells. RhoB depletion also reduces N-cadherin levels in PC3 cells, which do not express E-cadherin.ConclusionsThese results indicate that RhoB alters migration of cells with cell-cell adhesions by regulating cadherin levels. We propose that the relative contribution of integrins and cadherins to cell migration underlies the variable involvement for RhoB in this process and that the downregulation of RhoB in some epithelial cancers could contribute to the weakening of epithelial cell-cell junction during tumor progression.Electronic supplementary materialThe online version of this article (doi:10.1186/s12964-015-0085-y) contains supplementary material, which is available to authorized users.

Highlights

The Rho GTPase RhoB has been proposed to be a tumor suppressor in cancer and is downregulated in various tumors including prostate
RhoB regulates cell-cell adhesion in epithelial cells We have previously shown that RhoB depletion by RNAi alters focal adhesions and reduces β1 integrin levels in PC3 prostate cancer cells
To investigate whether RhoB could regulate cell-cell adhesions between epithelial cells, we depleted RhoB by RNAi in DU145 prostate cancer cells, which are epithelial in morphology and form colonies with E-cadherin-based adherens junctions [20,21]. siRNAs for RhoB were extensively used and characterized in our previous papers [15,22] and no change in RhoA or RhoC activity was observed after RhoB depletion

Summary

Introduction

The Rho GTPase RhoB has been proposed to be a tumor suppressor in cancer and is downregulated in various tumors including prostate. The Rho family of small GTPases are signalling molecules that regulate many cellular processes including cytoskeletal dynamics, cell motility, cell adhesion, cell division and transcription. They thereby contribute to wound healing, inflammation and cancer progression [1]. Most Rho family GTPases cycle between an active GTP-bound state and an inactive GDP-bound state Their activation is controlled by guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs), which activate or inactivate them respectively. In their active GTP-bound form, Rho GTPases interact with various downstream effectors to induce cellular responses.

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