Rab11 regulates E-cadherin expression and induces cell transformation in colorectal carcinoma

Abstract

BackgroundIn the process of epithelial mesenchymal transition EMT, the disassembly of junctional adhesion complexes such as E-cadherin is a remarkable sign during changes in cell morphology and polarity. However, E-cadherin expression is dynamic, and is regulated by the cellular endocytic system; it is also involved in cell signaling mechanisms. In this study, we investigated the role of E-cadherin in colorectal tumors and the relationship with recycling endosome protein Rab11 in colon cell transformation.MethodsFor tissue screening, the expressions of E-cadherin and Rab11 in colorectal tumors were identified by immunohistochemistry in 113 patients with colorectal carcinoma. For the in vitro cell experiment, GFP-tagged Rab11 plasmid was transfected into HT29 colon cells, E-cadherin expression and cell transformation were monitored by Western blot and confocal microscopy.ResultsIn immunohistochemistry, the mean score of E-cadherin in tumor and normal tissues was 1.41 ± 0.06 and 1.08 ± 0.06 (p < 0.05). The mean score of Rab11 in tumor and normal tissues was 0.51 ± 0.05 and 0.18 ± 0.02 (p < 0.05). Synchronous overexpression of E-cadherin and Rab11 was noted in 74 patients (66.5%) with colorectal carcinoma. When GFP-tagged Rab11 plasmid was overexpressed in cultured colon cell line HT-29, the E-cadherin expression was up-regulated, and cell membrane protrusion was induced, which resulted in cell transformation and cell migration.ConclusionsThis study demonstrated the importance of the overexpression of Rab11 and E-cadherin in colorectal cancer. The results indicated that Rab11 together with E-cadherin might be potential markers for colorectal cancer progression and treatment.

Interstitial fluid pressure regulates collective invasion in engineered human breast tumorsviaSnail, vimentin, and E-cadherin

“…We observed that aggregates with the highest frequency of collective invasion had elevated levels of both mesenchymal and epithelial markers, and that E-cadherin in particular promoted collective invasion, which suggests an additional role for EMT markers in the cellular response to physical cues such as IFP. These results are consistent with those from other studies showing that E-cadherin expression may actually enhance metastatic potential, 34, 39, 40 which contrasts with the classical view of E-cadherin as a tumor suppressor. 41–45 Remarkably, we found that E-cadherin was enriched in invading cohorts.…”

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

“…Cadherin‐based junctions between cells that maintain ‘supra cellular’ properties, such as collective polarization and force generation, have been claimed to characterize collective cell migration . Our histological study demonstrated dual overexpression of E‐cadherin and Rab11 in most carcinoma tissues with amorphous mass morphologies, and expression of both of these proteins in tumour nests has also been observed previously . These histological phenotypes have also previously been described in collective cell migration .…”

“…Solitary overexpression of Rab11 was found in 26 patients (23·0%), and solitary overexpression of E‐cadherin was found in 10 patients (8·9%). Only three patients (2·7%) lacked any overexpression of Rab11 and E‐cadherin . In the present study, the survival of the patients was further analysed, and the dual expression of the Rab11 and E‐cadherin was correlated with poor prognosis in CRC.…”

“…It has also been reported to participate in cellular functions and cancerous metastasis . Our previous work further demonstrated that Rab11 can regulate E‐cadherin expression during cell transformation in colon cancer . E‐cadherin has been reported to be important for collective cell migration; however, only one study in drosophila has so far demonstrated a role for Rab11 in collective cell migration .…”

“…E-cadherin, which functions in cell-cell adhesion, was previously thought to be a negative indicator of EMT. However, in many studies, E-cadherin expression has been positively correlated with the formation of many cancers, such as brain tumours, breast cancer and colon cancer [16][17][18][19][20][21]. E-cadherin has also been demonstrated to be critical for cell sphere formation and the anchorage-independent growth of cancer cells in collective cell migration [9,22,23].…”