Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
Volume 1864, Issue 4, Pages 1104-1114Publisher
ELSEVIER
DOI: 10.1016/j.bbadis.2018.01.011
Keywords
HSF1; PRC2; Methylation; ArgBP2; Gastric cancer
Funding
- National Natural Science Foundation of China [81372337, 81302221, 31201053, 31171360, 31371424, 31271389, 31571457]
- Ministry of Education of China [IRT 13101]
- Scientific Research Foundation of Liaoning Provincial Education Department [2013021090, LZ2015071]
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Arg Kinase-binding protein 2 (ArgBP2) is considered to be a scaffold protein that coordinates multiple signaling pathways converging on cell adhesion and actin cytoskeletal organization. It also plays an important role in blocking cancer metastasis as a potential tumor suppressor. However, its regulation mechanisms in tumor migration, especially in gastric cancer, are not fully understood. Here, we identified an ArgBP2 enhancer and showed that heat shock factor 1 (HSF1) directly interacted with microrchidia CW-type zinc finger 2 (MORC2) and bound to the enhancer of ArgBP2. HSF1 was found to promote proliferation, migration and invasion of gastric cancer cells. HSF1 or/and MORC2 increased recruitment of the polycomb repressive complex 2 (PRC2), particularly enhancer of zeste homolog 2 (EZH2), to the ArgBP2 enhancer and catalyzed tri-methylation of lysine 27 on histone H3 (H3K27me3), leading to transcriptional repression of ArgBP2. In addition, HSF1 and MORC2-induced migration and invasion in gastric cancer cells was dependent on ArgBP2 or EZH2. Clinical data exhibited a negative correlation of ArgBP2 with MORC2, HSF1, and EZH2. Our results thus contribute to the knowledge of the regulatory mechanism of HSF1 in down-regulating ArgBP2, providing new insight into the HSF1&MORC2-PRC2-ArgBP2 signaling pathway and a better understanding of their functions in gastric cancer cells.
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