Vega Francisco M, Thomas Mairian, Reymond Nicolas, Ridley Anne J
Randall Division of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus, London, SE1 1UL, UK.
Current address: Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Edificio IBiS, E-14013, Seville, Spain.
Cell Commun Signal. 2015 Jan 29;13:6. doi: 10.1186/s12964-015-0085-y.
The 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.
Here 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.
These 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.
Rho GTP酶RhoB被认为是癌症中的一种肿瘤抑制因子，在包括前列腺癌在内的多种肿瘤中表达下调。RhoB对细胞迁移的影响因细胞类型和条件而异，但其变异性的分子基础尚不清楚。RhoB调节膜受体和整合素的运输。我们之前已经表明，在PC3前列腺癌细胞中，RhoB的缺失会改变粘着斑动力学并降低β1整合素的表面水平，这与迁移速度增加相关。
在这里我们表明，在DU145前列腺癌细胞中，RhoB的缺失会降低细胞间粘附并下调E-钙粘蛋白水平，同时增加内化的E-钙粘蛋白，这伴随着迁移速度的增加。在DU145细胞中，RhoB与E-钙粘蛋白一起定位于细胞间连接。RhoB的缺失也会降低PC3细胞中N-钙粘蛋白的水平，PC3细胞不表达E-钙粘蛋白。
这些结果表明，RhoB通过调节钙粘蛋白水平来改变具有细胞间粘附的细胞的迁移。我们提出，整合素和钙粘蛋白对细胞迁移的相对贡献是RhoB在此过程中不同参与程度的基础，并且在一些上皮性癌症中RhoB的下调可能导致肿瘤进展过程中上皮细胞间连接的减弱。
