Negative regulator of oncoprotein YAP1 in the Hippo signaling pat

Negative regulator of oncoprotein YAP1 in the Hippo signaling pathway plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. LATS1 phosphorylates YAP1 protein and inhibits its translocation into the nucleus to regulate cellular genes important

for cell proliferation, cell death, and cell migration [19]. Furthermore, in previous studies LATS1 overexpression induced cell apoptosis by increasing pro-apoptotic proteins p53 and Bax [11] and suppressed cell proliferation through p53 upregulation to ensure genomic integrity [20]. Conversely, knockdown of LATS1 induced cell migration in HeLa cells [21]. These results together supported that LATS1 played a suppressive role in tumor pathogenesis. In order to assess the role of LATS1 in glioma, we first performed real-time PCR to measure Trichostatin A in vitro the expression of LATS1 mRNA transcripts in 17 paired glioma samples and their adjacent

brain tissues. Similar to reports of other tumor types [13, 14], we observed that LATS1 expression find more was significantly decreased in 13 glioma tissues compared to their matched normal tissues. This suggested LATS1 functions as a tumor suppressor in glioma. We validated this downregulation of LATS1 protein by immunohistochemistry. In addition, we found that LATS1 expression levels were inversely associated with WHO grade of glioma and KPS. Further, we presented the evidence that LATS1 protein expression in glioma was positively correlated with patient’s overall survival. The patients with lower expression of LATS1 protein had shorter survival time. According to multivariate analyses, decreased expression of LATS1 protein was a significant predictor of poor prognosis for glioma patients. These results were analogous to Takahashi et al’s report in the study of breast cancer [13] and strongly suggested a suppressive role of LATS1 in glioma tumorigenesis. Next, we used a

gain-of-function approach by introducing the LATS1 gene into LATS1-negative U251 glioma cells, to investigate Amrubicin its biological functions. We observed that overexpression of LATS1 caused significant reduced in vitro cell growth and G(2)/M arrest. These are consistent with the findings by Yang et al. [11] and Xia et al.[12] that upregulation of LATS1 suppresses cell growth and cell cycle progression, which further demonstrates that the suppressive biological functions of LATS1 are common to multiple cancers. Additionally, our study also revealed a novel function of LATS1 in glioma in suppression of cell migration and invasion. This suggests LATS1 may be involved in invasion and metastasis of cancer, a concept which would need to be MI-503 manufacturer confirmed by in vivo animal model. The observations that LATS1 regulates multiple cellular processes such as cell proliferation, cell cycle progression, migration, invasion emphasizes its importance as a therapeutic target for treating glioma.

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