Expression of LATS1 contributes to good prognosis and can negatively regulate YAP oncoprotein in non-small-cell lung cancer

Abstract

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.

The Hippo pathway in colorectal cancer

“…Phosphorylation β loss of function in prostate cancer [119], CCL: overexpression inhibits cell proliferation and promote apoptosis in HepG2 cells [87] Mouse double KO: cholangiocarcinoma [46,101], HCC [120] Decreased mRNA level in tumour associated with node metastasis [121], mouse double KO: crypt dysplasia, colon adenoma [46,78,120] RASSF1, RASSF1A TSG: promoter hypermethylation and decrease expression in cancer: thyroid [122], oesophageal [123], prostate [124], colorectal, breast [125] TSG; promoter hypermethylation and decrease expression in CRC [126,127] SAV1, Salvador TSG: LOH and downregulation in renal cell carcinoma [128], no gene mutation in stomach, liver and lung cancer [129] CCL: overexpression induces apoptosis in MCF-7 cells [130] No gene mutation in CRC [129] LATS1 TSG: decrease expression in cancer: glioma [131], NSLC [132], sarcoma [133] and astrocytoma [134]. CCL: LATS1 degradation inhibits apoptosis in MCF10A cells [135] TSG: promoter hypermethylation and mRNA decrease in CRC [86] LATS2 TSG: decrease expression in: malignant mesothelioma (and LOH) [136], NSLC (no mutation found) [137] and astrocytoma [134] OG: overexpression in AML [138], nosopharyngeal carcinoma [139] TSG: downregulation in CRC [87] …”

Down-regulation of LATS2 in non-small cell lung cancer promoted the growth and motility of cancer cells

“…Decreased expression of LATS2 is seen in prostate cancer tissues [23,24]. Previous studies have found that LATS1 inhibited the proliferation and invasion of NSCLC cells [24]. However, the function of LATS2 in NSCLC has not been well studied.…”

“…Dysregulation of LATS1 and/or LATS2 has been implicated in soft tissue sarcomas, leukemia, astrocytoma, and in cancers of the breast, prostate, lung, liver, and esophagus [17][18][19][20][21][22][23]. Decreased expression of LATS2 is seen in prostate cancer tissues [23,24]. Previous studies have found that LATS1 inhibited the proliferation and invasion of NSCLC cells [24].…”

Expression of LATS family proteins in ovarian tumors and its significance

“…The family includes 2 members, LATS1 and LATS2, which play important roles in the control of tumor development [4,5] and cell cycles through multiple mechanisms and signaling pathways, including those of p53 [6][7][8], Hippo, and Wnt [9]. Although LATS proteins are reportedly down-regulated in many types of cancer such as breast carcinoma [10] and nonsmall cell lung cancer [11], they are overexpressed in nasopharyngeal carcinoma [12]. Thus, whether LATS family proteins are indeed tumor suppressors remains controversial.…”