Tumor Suppressor LKB1 inhibits both the mRNA Expression and the Amplification of hTERC by the Phosphorylation of YAP in Lung Cancer Cells
Tumor Suppressor LKB1 inhibits both the mRNA Expression and the Amplification of hTERC by the Phosphorylation of YAP in Lung Cancer Cells
复制标题
肿瘤抑制因子 LKB1 通过 YAP 磷酸化抑制肺癌细胞中 hTERC 的 mRNA 表达和扩增
DOI：
10.7150/jca.33237
复制
发表时间：
2019-01-01
影响因子：
3.9
通讯作者：
Wu, Guang-Ping
中科院分区：
文献类型：
--
作者：
He, Ling;Wu, Ming-Zhe;Wu, Guang-Ping
肝激酶B1 （LKB1）是一种重要的肿瘤抑制因子，在人类癌症中经常发生突变。LKB1具有丝氨酸/苏氨酸蛋白激酶活性，通过磷酸化Yes-Associated protein （YAP）调控基因表达。磷酸化依赖性YAP穿梭是Hippo通路中至关重要的细胞内机制。在我们前期的研究中，我们发现肺癌患者支气管刷毛细胞中hTERC的扩增量明显增高，但其分子机制尚不清楚。在本研究中，我们发现LKB1过表达可以磷酸化YAP并促进其核排斥。沉默LKB1可以使YAP去磷酸化并促进其进入细胞核。我们发现LKB1抑制mRNA的表达和hTERC的扩增。YAP在mRNA和基因扩增水平上进一步上调hTERC。因此，我们认为LKB1可能通过LKB1- pyap (YAP)-hTERC轴抑制hTERC的表达和扩增。
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.