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 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 G(0)/G(1) 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.