J Cancer 2019; 10(16):3632-3638. doi:10.7150/jca.33237

Research Paper

Tumor Suppressor LKB1 inhibits both the mRNA Expression and the Amplification of hTERC by the Phosphorylation of YAP in Lung Cancer Cells

Ling He1, Ming-Zhe Wu2, Xu-Bo Wang3, Xue-Shan Qiu1, En-Hua Wang1, Guang-Ping Wu1✉

1. Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang 110001, China
2. Department of Gynecology, The First Hospital of China Medical University, Shenyang 110001, China
3. Department of Pathology, Xuzhou City Hospital of TCM, Nanjing University of Chinese Medicine, Xuzhou 221000, China

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Citation:
He L, Wu MZ, Wang XB, Qiu XS, Wang EH, Wu GP. Tumor Suppressor LKB1 inhibits both the mRNA Expression and the Amplification of hTERC by the Phosphorylation of YAP in Lung Cancer Cells. J Cancer 2019; 10(16):3632-3638. doi:10.7150/jca.33237. Available from http://www.jcancer.org/v10p3632.htm

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Abstract

Liver kinase B1 (LKB1) is a critical tumor suppressor that is frequently mutated in human cancers. LKB1 has serine/threonine protein kinase activity, which regulates gene expression by phosphorylation of Yes-Associated protein (YAP). The phosphorylation-dependent YAP shuttling is critically important intracellular mechanism in the Hippo pathway. In our previous study, we found that the amplification of hTERC was significant higher in the bronchial brushing cells of patients with lung cancer, however, the underlying molecular mechanism is not clear. In this study, we showed that LKB1 overexpression could phosphorylate YAP and promoted its nuclear rejection. Silencing LKB1 could dephosphorylate YAP and promoted its entry into the nucleus. Here, we found that LKB1 inhibited the mRNA expression and the amplification of hTERC. YAP further up-regulated hTERC at mRNA and gene amplification levels. Therefore, we suggest that LKB1 may inhibit the expression and amplification of hTERC through the axis of LKB1-pYAP(YAP)-hTERC.

Keywords: liver kinase B1, yes-associated protein (YAP), human telomere RNA (hTERC), lung cancer