Overexpression of LRIG1 regulates PTEN via MAPK/MEK signaling pathway in esophageal squamous cell carcinoma.

Abstract

The present study aimed to evaluate the role of leucine-rich repeats and immunoglobulin-like domain protein 1 (LRIG1) in the regulation of phosphatase and tensin homolog (PTEN) expression in esophageal carcinogenesis. LRIG1 was overexpressed in esophageal squamous cell carcinoma (ESCC) cell lines, and the effect of LRIG1 overexpression on the mRNA and protein expression levels of PTEN was evaluated by reverse transcription-quantitative polymerase chain reaction and western blotting. Furthermore, the effects of LRIG1 overexpression on the cell cycle distribution and apoptosis of ESCC cells were examined by flow cytometry. Various cell signaling pathway inhibitors were used to assess the effects of LRIG1 on downstream signaling in ESCC cell lines. In addition, the association between LRIG1 and PTEN expression was examined in 48 samples from patients with ESCC. LRIG1 overexpression was demonstrated to downregulate PTEN expression in ESCC cell lines, and promote their proliferation and inhibit apoptosis. In addition, LRIG1-mediated suppression of PTEN expression was inhibited by the U0126 inhibitor, which suggests that LRIG1 may inhibit the activation of PTEN signaling molecules by triggering the mitogen-activated protein kinase (MAPK)/MAPK kinase 1 (MEK) signaling pathway. In conclusion, the present study demonstrated that overexpression of LRIG1 significantly and adversely affected the survival of ESCC cells, and that the MAPK/MEK signaling pathway may be responsible for the repression of PTEN expression and function.