Tumor suppressor LKB1 inhibits the progression of gallbladder carcinoma and predicts the prognosis of patients with this malignancy

  • Authors:
    • Ming-Tai Hu
    • Jing-Han Wang
    • Yong Yu
    • Chen Liu
    • Bin Li
    • Qing-Bao Cheng
    • Xiao-Qing Jiang
  • View Affiliations

  • Published online on: July 2, 2018     https://doi.org/10.3892/ijo.2018.4466
  • Pages: 1215-1226
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Abstract

Gallbladder carcinoma (GBC) represents the most common fatal tumors of the biliary tract. The 3-year or 5-year survival rate for patients with this disease are 30 and 5%, respectively. Liver kinase B1 (LKB1), a primary upstream kinase of adenosine monophosphate-activated protein kinase (AMPK) necessary for maintaining cell metabolism and energy homeostasis, has been found to be an important tumor suppressor gene in recent years, and its inactivation has also found to be closely associated with tumor growth, metastasis and cancer stem cell (CSC) proliferation. Nevertheless, the function of LKB1 in GBC remains unclear. In this study, we found that the expression of LKB1 in GBC tissues was decreased compared with that in non-cancerous tissues. LKB1 overexpression suppressed the proliferation, metastasis and expansion of GBC CSCs. Mechanically, LKB1 suppressed GBC cell progression via the JAK/signal transducer and activator of transcription 3 (STAT3) pathway. The use of the JAK2 inhibitor, AZD‑1480, attenuated the suppressive effects of LKB1 overexpression on the growth, metastasis and self-renewal ability of the GBC cells, which further demonstrated that JAK/STAT3 was involved in the LKB1-induced suppression of GBC cell growth, metastasis and self-renewal ability. More importantly, the decreased expression of LKB1 was a predictor of a poor prognosis of patients with GBC. On the whole, our data indicate that LKB1 inhibits GBC cell growth, metastasis and self-renewal ability by disrupting JAK/STAT3 signaling, and may thus prove to be a novel prognostic biomarker for patients with GBC.
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September-2018
Volume 53 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Hu M, Wang J, Yu Y, Liu C, Li B, Cheng Q and Jiang X: Tumor suppressor LKB1 inhibits the progression of gallbladder carcinoma and predicts the prognosis of patients with this malignancy. Int J Oncol 53: 1215-1226, 2018
APA
Hu, M., Wang, J., Yu, Y., Liu, C., Li, B., Cheng, Q., & Jiang, X. (2018). Tumor suppressor LKB1 inhibits the progression of gallbladder carcinoma and predicts the prognosis of patients with this malignancy. International Journal of Oncology, 53, 1215-1226. https://doi.org/10.3892/ijo.2018.4466
MLA
Hu, M., Wang, J., Yu, Y., Liu, C., Li, B., Cheng, Q., Jiang, X."Tumor suppressor LKB1 inhibits the progression of gallbladder carcinoma and predicts the prognosis of patients with this malignancy". International Journal of Oncology 53.3 (2018): 1215-1226.
Chicago
Hu, M., Wang, J., Yu, Y., Liu, C., Li, B., Cheng, Q., Jiang, X."Tumor suppressor LKB1 inhibits the progression of gallbladder carcinoma and predicts the prognosis of patients with this malignancy". International Journal of Oncology 53, no. 3 (2018): 1215-1226. https://doi.org/10.3892/ijo.2018.4466