Cytokeratin 18 knockdown decreases cell migration and increases chemosensitivity in non-small cell lung cancer.

ABSTRACT

PURPOSE: Cytokeratin 18 (CK18) is a structural protein that is normally expressed in many single-layer epithelia. Previous studies have indicated that aberrant CK18 expression is associated with cancer progression. However, the functions of CK18 in lung cancer have not been fully elucidated. Here, we investigate the roles of CK18 in non-small cell lung cancer (NSCLC). METHODS: CK18 protein expression was evaluated by immunohistochemistry in a lung cancer tissue microarray containing 129 cancer samples, and correlations between CK18 expression and clinicopathological characteristics and prognosis were analyzed. We then studied the effects of CK18 knockdown on cell motility and chemosensitivity in lung cancer cells. RESULTS: High CK18 expression was detected in 101/129 (78.3 %) lung cancers. CK18 expression was significantly correlated to clinical stage, lymph node metastasis, the number of pathologically positive lymph nodes and recurrence and metastasis. Kaplan-Meier survival analysis showed that CK18 was a prognostic factor for overall survival (P = 0.016) and disease-free survival (P = 0.014). In addition, CK18 knockdown decreased cell migration and enhanced the sensitivity of lung cancer cells to paclitaxel. CONCLUSIONS: These findings indicate that CK18 plays an important role in lung cancer progression and may be a therapeutic target for NSCLC.