LIM and SH3 protein 1 knockdown suppresses proliferation and metastasis of colorectal carcinoma cells via inhibition of the mitogen-activated protein kinase signaling pathway

LIM 和 SH3 蛋白 1 敲低可通过抑制丝裂原活化蛋白激酶信号通路抑制结直肠癌细胞的增殖和转移

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作者:Hongpeng Zhao, Bo Liu, Jie Li

Abstract

LIM and SH3 protein 1 (Lasp-1), a focal adhesion protein, serves a critical role in the regulation of cell proliferation and migration. The role of Lasp-1, as well as the intracellular signaling pathways involved in metastasis and progression of colorectal carcinoma, remains unclear. In the present study, the regulatory effect of Lasp-1 and the underlying molecular mechanism involved in migration and invasion of colorectal carcinoma were investigated. RNA interference and overexpression in SW480 cells were performed to elucidate the role of Lasp-1. Reverse transcription-quantitative polymerase chain reaction, western blotting and immunofluorescence were conducted to determine the mRNA and protein levels of Lasp-1 and extracellular-signal-regulated kinase 1/2 (ERK1/2) in SW480 cells as well as tumor and adjacent normal tissues obtained from 20 patients with colorectal carcinoma. Furthermore, a cell proliferation assay, flow cytometric analysis, and cell migration and invasion assays were performed to examine the effect of Lasp-1 on cell growth. The results of the present study demonstrated that Lasp-1 and ERK1/2 were upregulated in tumor tissue compared with adjacent normal colorectal mucosa. Cell-based in vitro assays demonstrated that Lasp-1 knockdown suppressed the expression and activation of ERK1/2, whereas Lasp-1 overexpression resulted in ERK1/2 upregulation. Additionally, Lasp-1 knockdown inhibited cell proliferation, migration, and invasion and induced cellular apoptosis and G0/G1 cell-cycle arrest. The results of the present study indicate that Lasp-1 serves a critical role in the progression of colorectal carcinoma regulating the activation of the mitogen-activated protein kinase signaling pathway.

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