Author Description

This dissertation, "The Role of Large Tumor Suppressor 2 Gene in Non-small Cell Lung Cancer" by Yang, Luo,, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Adenocarcinoma (AD) is the predominant subtype of non-small cell lung cancer (NSCLC). Due to the high mortality rate, extensive efforts have been devoted to unravel driver mutations and targetable biomarkers in attempt to improve diagnosis and treatment of lung AD. Being first identified in the Hippo pathway, large tumor suppressor 2 (LATS2) kinase has been shown to play critical roles in multiple biological processes known to be important in carcinogenesis, including cell proliferation, cell differentiation, apoptosis, cell migration and invasion. Aberrant expression of LATS2 has been reported in primary cancer from lung and other solid organ tumors. The expression status and the functional roles of LATS2 kinase in lung AD have not been explored. In the first part of this study, the expression levels of LATS2 in primary lung AD samples were assessed. LATS2 mRNA level was found to be an independent predictor for progression free survival (DFS) as well as overall survival (OS) in patients with resected pulmonary AD. Furthermore, down-regulation of LATS2 in some lung AD cell lines promoted the phosphorylation status of Erk1/2 and Akt, and it also modulated the expression of p53. In the second part, in vitro silencing of LATS2 by specific siRNA duplexes altered the levels of apoptosis in response to serum deprivation. The magnitude of this regulation depended on cancer cell LATS2 kinase could play a role in facilitating apoptosis in cells sensitive to low