Open AccessCytoplasmic liver kinase B1 promotes the growth of human lung adenocarcinoma by enhancing autophagy
Author(s) -
Liu Mengjie,
Jiang Lili,
Fu Xiao,
Wang Wenjuan,
Ma Jiequn,
Tian Tao,
Nan Kejun,
Liang Xuan
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13746
Subject(s) - cytoplasm , autophagy , a549 cell , adenocarcinoma , biology , cancer research , cell growth , apoptosis , microbiology and biotechnology , chemistry , cancer , biochemistry , genetics
Liver kinase B1 ( LKB 1 ) as a tumor suppression gene that is associated with various kinds of cancers, including lung cancer. In this study, we found that the effect of LKB 1 on tumor growth was dependent on its subcellular expression in A549 and HCC 827 cells. Full‐length LKB 1 decreased the proliferation and clonogenicity of A549‐ LKB 1 and HCC 827‐ LKB 1 cells, but increased their apoptosis. Opposite effects were observed in A549‐ LKB 1 s and HCC 827‐ LKB 1 S cells that overexpressed truncated LKB 1 without the nuclear localization sequence. The truncated cytoplasmic LKB 1 enhanced the growth of implanted tumors in vivo. The truncated cytoplasmic LKB 1 promoted autophagy, which was independent of AMP ‐activated protein kinase and mTOR signaling in A549 and HCC 827 cells. Further characterization indicated that higher levels of cytoplasmic LKB 1 expression were associated with advanced TNM stage and reduced overall survival (OS) in 190 patients with adenocarcinoma. In contrast, high nuclear expression of LKB 1 is associated with early TNM stage and longer OS . The high level of cytoplasmic LKB 1 expression was an independent risk factor for poor overall survival in patients with adenocarcinoma. Together, our results revealed that cytoplasmic LKB 1 promotes the growth of lung adenocarcinoma and could be a prognostic marker for lung adenocarcinoma.