Large tumor suppressor (LATS) is a Ser/Thr kinase originally isolated from Drosophila. Recent studies demonstrate that LATS is an important member of the Hippo pathway which can regulate organ size and cell proliferation. However, little is known about the expression and clinical significance of LATS in lung cancer. In this study, we aimed to assess the clinical significance and biological functions of LATS1 in non-small-cell lung cancer (NSCLC). We investigated the expression of LATS1 in 136 cases of NSCLC tissue and 30 cases of normal lung tissue by immunohistochemical staining. The results confirmed that LATS1 expression was higher in normal lung tissues, but significantly lower in NSCLC tissues. Moreover, the expression of LATS1 in NSCLC was significantly correlated with p-TNM stage (p = 0.038) and lymph node metastasis (p = 0.014). Importantly, the loss of LATS1 expression was associated with short overall survival. Further study in NSCLC cell lines in which LATS1 was either overexpressed or depleted confirmed that LATS1 markedly inhibited cell proliferation and invasion and could regulate the nuclear location of yes-associated protein (YAP). These results indicate that LATS1 may play an important role in NSCLC, and may serve as a novel therapeutic target of NSCLC.
Therefore, this study demonstrates that the expression pattern of p120ctn is associated with acquired resistance to EGFR-TKIs in lung cancer, providing information toward addressing the problem of drug resistance in patients with non-small cell lung cancer.
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