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Poster Display session (Friday) (ID 65)
- Event: ELCC 2018
- Type: Poster Display session
- Presentations: 1
- Coordinates: 4/13/2018, 12:30 - 13:00, Hall 1
179P - The cytoplasmic LKB1 promotes the growth of human lung adenocarcinoma by enhancing autophagy (ID 342)
12:30 - 13:00 | Presenting Author(s): M.J. Liu
Liver Kinase B1 (LKB1), as a tumor suppression gene, is associated with various kinds of cancers, including lung cancer. However, it is unclear whether LKB1 can be also located in the nucleus of NSCLC cells and if yes, what its function is during the development and progression of NSCLC.
Full length LKB1 (LKB1~L~) and LKB1 without nuclear localization signal (LKB1~S~) were introduced into lung adenocarcinoma cell A549 respectively. MTT assays, colony formation assays, flow cytometry analysis, transmission electron microscopy and western blot were used to evaluate the effect of LKB1~L~ and LKB1~S~ in vitro. The subcutaneous tumor model in nude mice was used to evaluate the effect of LKB1~L~ and LKB1~S~ in vivo. The expression profile of LKB1 was examined in 190 lung adenocarcinoma tissues by immunohistochemistry and was analyzed combined with clinical parameters.
In this study, we found that cytoplasmic LKB1 promoted the growth of lung adenocarcinoma by enhancing autophagy and it was independent of the AMPK/mTOR signaling. In 190 lung adenocarcinoma samples, we found that LKB1 was expressed in both the nucleus and cytoplasm of lung adenocarcinoma cells and the levels of nuclear LKB1 were inversely associated the levels of cytoplasmic LKB1 in lung adenocarcinoma tissues. Furthermore, the different subcellular localizations of LKB1 were correlated with opposite clinical parameters in this population. While the cytoplasmic LKB1 expression was associated with poor differentiation and advanced TNM stage, the nuclear LKB1 expression was related to well differentiation and early TNM stage. Moreover, the cytoplasmic LKB1 was associated with poor OS in this population and was an independent risk factor for prognosis.
In summary, our data demonstrated that the cytoplasmic LKB1 without nuclear localization signal promoted A549 cell survival in vitro and lung tumor growth in vivo. Furthermore, the cytoplasmic LKB1 was associated with poor prognosis in lung adenocarcinoma cancer. Therefore, our findings may provide new insights into the pathogenesis of lung adenocarcinoma and novel biomarkers for prognosis of lung adenocarcinoma.
Clinical trial identification:
Legal entity responsible for the study:
The First Affiliated Hospital of Xi'an Jiaotong University
Has not received any funding
All authors have declared no conflicts of interest.