Engulfment and Cell Motility1 Regulate Tumor Cell Behaviors and Predict Prognosis in Colorectal Cancer

Abstract Background: Engulfment and cell motility 1 (ELMO1) plays a crucial role in the process of migration, chemotaxis, and metastasis of tumor cells. ELMO 1 has been implicated in the pathogenesis of various cancers. However, the distinct function of ELMO1 in colorectal cancer (CRC) is unclear. We determined whether ELMO1 affected the oncogenic behavior of CRC cells and investigated its prognostic value in CRC patients. Methods: We investigated the impact of ELMO1 on tumor cell behaviors using small interference RNA in CRC cell lines, including SW480 and DLD1. The expression of ELMO1 was investigated by reverse transcription-polymerase chain reaction, immunohistochemistry, and enzyme-linked immunosorbent assay in cancer tissues and sera taken from CRC patients. Results: ELMO1 knockdown suppressed tumor cell proliferation in SW480 and DLD1 cells. ELMO1 knockdown-induced apoptosis through up-regulation of caspase-3, -7, and PARP activities and down-regulation of the anti-apoptotic Mcl-1 protein. ELMO1 knockdown-induced cell cycle arrest by decreasing cyclin D1, cyclin-dependent kinase 2, 4 and 6, and the 25C cell division cycle (CDC25C). ELMO1 knockdown suppressed tumor cell invasion and migration. The expression of E-cadherin was increased, and Vimentin and Claudin 1 decreased with ELMO1 knockdown. The phosphorylation levels of PDK1, Akt, and GSK-3β and were down-regulated by ELMO1 knockdown. The expression of ELMO1 was up-regulated in cancer tissues and sera taken from CRC patients. ELMO1 expression was significantly associated with tumor stage, lymph node metastasis, distant metastases, and poor survival. Conclusions: These results indicate that ELMO1 mediates tumor progression by increasing tumor cell motility and inhibiting apoptosis in human CRC.