Abstract
BackgroundLATS2, which encodes a novel serine/threonine kinase, is known to be important in centrosome duplication and in the maintenance of genomic stability. Recently, a potential role for LATS2 in cancer has been reported. In breast cancer and acute lymphoblastic leukemia (ALL), LATS2 mRNA is downregulated and has been suggested to be a tumor suppressor. However, the role of LATS2 in nasopharyngeal carcinoma has not been investigated. In this study, we aimed to investigate the expression pattern of LATS2 and its clinicopathological involvement in nasopharyngeal carcinoma to understand its effect on cell survival.MethodsUsing quantitative real time PCR and immunoblotting, the expression of LATS2 was detected in nasopharyngeal carcinoma cell lines and in the immortalized nasopharyngeal epithelial cell line NP69. Using immunohistochemistry, we analyzed LATS2 protein expression in 220 nasopharyngeal carcinoma cases. The association of LATS2 protein expression with the clinicopathological characteristics and the prognosis of nasopharyngeal carcinoma were subsequently assessed. Using methylation specific PCR, we detected the methylation status of the LATS2 promoter. RNA interference was performed by transfecting siRNA to specifically knock down LATS2 expression in 5-8F and CNE2.ResultsLATS2 protein was detected in 178 of 220 (80.91%) cases of nasopharyngeal carcinoma. LATS2 overexpression was a significant, independent prognosis predictor (P = 0.037) in nasopharyngeal carcinoma patients. Methylation specific PCR revealed that 36.7% (11/30) of nasopharyngeal carcinoma tissues and all of the chronic nasopharyngeal inflammation samples were methylated. Functional studies showed that the suppression of LATS2 expression in nasopharyngeal carcinoma (5-8F and CNE2) cell lines by using specific small interfering (siRNA) resulted in the inhibition of growth, induction of apoptosis and S-phase cell cycle increase. Overexpression of LATS2 in NP69 stimulated cell proliferation.ConclusionsOur results indicate that LATS2 might play a role in the tumorigenesis of nasopharyngeal carcinoma by promoting the growth of nasopharyngeal carcinoma cells. Transfection with specific siRNA might be feasible for the inhibition of growth, induction of apoptosis and S phase increase in nasopharyngeal carcinoma.
Highlights
LATS2, which encodes a novel serine/threonine kinase, is known to be important in centrosome duplication and in the maintenance of genomic stability
Overexpression of LATS2 stimulated cell growth. These results suggest that LATS2 might play a role in the tumorigenesis of Nasopharyngeal carcinoma (NPC) and might be a potential therapeutic target in NPC treatment
Compared to NP69 cells, overexpression of LATS2 mRNA was observed in the NPC cell lines CNE1, CNE2, 5-8F and C666-1
Summary
LATS2, which encodes a novel serine/threonine kinase, is known to be important in centrosome duplication and in the maintenance of genomic stability. We aimed to investigate the expression pattern of LATS2 and its clinicopathological involvement in nasopharyngeal carcinoma to understand its effect on cell survival. LATS2 (Large Tumor Suppressor homolog 2), known as Kpm, is one of the two human homologues of Drosophila wts, which is a component of the Hippo pathway. This pathway is known to control organ size by modulating cell growth, proliferation, and apoptosis [13,14]. LATS2 binds to Mdm and inhibits its E3 ubiquitin ligase activity, resulting in the stabilization of p53 in nocodazole treated cells, while p53 rapidly and selectively up-regulates LATS2 expression in G2/M cells. In LATS2-/- embryos, the development of the nervous system was severely impaired, and deficiency in LATS2 results in growth arrest and apoptosis
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