Overexpression of small GTPases directly correlates with expression of δ‐catenin and their coexpression predicts a poor clinical outcome in nonsmall cell lung cancer

Abstract

δ-catenin can affect cytoskeletal assembly, and promote cell migration by regulating the activity of small GTPases. While many malignancies have been shown to be positive for δ-catenin, it is still unclear whether δ-catenin and small GTPases are coexpressed in tumor cells, and so is the relationship between their coexpression and prognosis in the tumor patients. In this study, immunohistochemistry was performed to examine expressive levels of δ-catenin, cdc42, and Rac1 in 135 cases of nonsmall cell lung cancer (NSCLC), including 60 cases with follow-up records. Thirty samples of paired lung cancer tissues and adjacent normal lung tissues were collected to analyze mRNA and protein expression of δ-catenin and small GTPases. The effects of δ-catenin on small GTPases expression and invasive ability of lung cancer cells were also evaluated. Compared with normal lung tissues, both mRNA and protein levels of δ-catenin and small GTPases were increased in lung cancer tissues (P < 0.05), and the expression of small GTPases directly correlated with that of δ-catenin (P < 0.001). In addition, δ-catenin and small GTPases tended to be coexpressed in lung adenocarcinoma, advanced stages, and primary tumors with lymph node metastasis (all P < 0.05). The patients with coexpression of δ-catenin and small GTPases had a shorter survival time than those without coexpression (P < 0.05). Furthermore, δ-catenin overexpression could enhance invasive ability of lung cancer cells by upregulating protein and transcriptional level of small GTPases. Therefore, δ-catenin likely upregulates the activity of small GTPases at transcriptional level, and their coexpression may predict a poor clinical outcome in NSCLC patients.