Rab11 collaborates E-cadherin to promote collective cell migration and indicates a poor prognosis in colorectal carcinoma.

Abstract

Collective cell migration, whereby the cell-cell contacts such as E-cadherin are maintained during migration, has only recently emerged, and its detailed mechanisms are still unclear. In this study, the role of Rab11, which functions in recycling endosomes, and its relationship to E-cadherin in colorectal carcinoma were identified, and the role of Rab11 in the collective cell migration of colon cancer cells was clarified. A total of 107 patients with surgically resected colorectal carcinoma were enrolled in this immunohistochemical study. Relationships between the overexpression of Rab11 and E-cadherin and survival were evaluated. The cell biology of Rab11 overexpression or knock-down in HT-29 colon cells was studied. The expression of Rab11 and E-cadherin was not correlated with the stage of cancer or lymph node metastasis. However, the overall survival was poor in the group of 67 patients with duo-positive Rab11 and E-cadherin expression compared to the group (40 patients) without dual-positive expression (P = 0·038). Rab11 was demonstrated to have a physical interaction with E-cadherin, and overexpression of Rab11 was found to promote collective cell migration through the increased distribution of E-cadherin, which enhanced cell-cell connections. In addition, Rac1 activation and matrix metalloproteinase-2 expressions were upregulated upon Rab11 expression. This study demonstrated that Rab11 and E-cadherin expressions are indicators of poor survival time in colorectal carcinoma, but that Rab11 overexpression may contribute to increased collective cell invasion in colorectal carcinoma.