Li Shujun, Qin Xuebo, Chai Song, Qu Changbao, Wang Xiaolu, Zhang Helin
Department of Thoracic Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, 050051, China.
Department of Thoracic Surgery, Hebei Chest Hospital, Shijiazhuang, 050051, China.
Sci Rep. 2016 Feb 22;6:21713. doi: 10.1038/srep21713.
Losing the E-cadherin plays an important role in the metastasis of cancer. The regulation of the expression of E-cadherin is unclear. Circadian rhythm alteration is associated with the pathogenesis of a number of cancers. This study aims to investigate the role of one of the circadian proteins, period-2 (Per2) in repressing the expression of E-cadherin in esophageal cancer (esophageal cancer). We observed that the levels of circadian protein Per2 were significantly increased and E-cadherin was significantly decreased in the tissue of human esophageal cancer with metastasis as compared with non-metastatic esophageal cancer. Overexpression of Per2 in the esophageal cancer cells markedly repressed the expression of E-cadherin. The pHDAC1 was detected in human esophageal cancer with metastasis, which was much less in the esophageal cancer tissue without metastasis. Overexpression of Per2 increased the levels of pHDAC1 as well as the E-cadherin repressors at the E-cadherin promoter locus. Overexpression of Per2 markedly increased the migratory capacity of esophageal cancer cells, which was abolished by the inhibition of HDAC1. We conclude that Per-2 plays an important role in the esophageal cancer cell metastasis, which may be a novel therapeutic target for the treatment of esophageal cancer.
E-钙黏蛋白的缺失在癌症转移中起重要作用。E-钙黏蛋白表达的调控尚不清楚。昼夜节律改变与多种癌症的发病机制相关。本研究旨在探讨一种昼夜节律蛋白周期蛋白2（Per2）在抑制食管癌中E-钙黏蛋白表达方面的作用。我们观察到，与非转移性食管癌相比，发生转移的人食管癌组织中昼夜节律蛋白Per2水平显著升高，而E-钙黏蛋白显著降低。在食管癌细胞中过表达Per2可显著抑制E-钙黏蛋白的表达。在发生转移的人食管癌中检测到磷酸化组蛋白去乙酰化酶1（pHDAC1），在无转移的食管癌组织中则少得多。Per2的过表达增加了pHDAC1的水平以及E-钙黏蛋白启动子位点处E-钙黏蛋白抑制因子的水平。Per2的过表达显著增加了食管癌细胞的迁移能力，而组蛋白去乙酰化酶1（HDAC1）的抑制可消除这种能力。我们得出结论，Per-2在食管癌细胞转移中起重要作用，这可能是治疗食管癌的一个新的治疗靶点。
