한빛사 논문
Minjeong Jang, Jinhyeon An, Seung Won Oh, Joo Yeon Lim, Joon Kim, Jung Kyoon Choi, Jae-Ho Cheong & Pilnam Kim
Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
Minjeong Jang, Jinhyeon An, Seung Won Oh, Jung Kyoon Choi & Pilnam Kim
Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
Joo Yeon Lim & Jae-Ho Cheong
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
Joon Kim
Institute for Health Science and Technology, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
Pilnam Kim
Correspondence to Jung Kyoon Choi or Jae-Ho Cheong or Pilnam Kim.
Abstract
In many cancers, tumour progression is associated with increased tissue stiffness. Yet, the mechanisms associating tissue stiffness with tumorigenesis and malignant transformation are unclear. Here we show that in gastric cancer cells, the stiffness of the extracellular matrix reversibly regulates the DNA methylation of the promoter region of the mechanosensitive Yes-associated protein (YAP). Reciprocal interactions between YAP and the DNA methylation inhibitors GRHL2, TET2 and KMT2A can cause hypomethylation of the YAP promoter and stiffness-induced oncogenic activation of YAP. Direct alteration of extracellular cues via in situ matrix softening reversed YAP activity and the epigenetic program. Our findings suggest that epigenetic reprogramming of the mechanophysical properties of the extracellular microenvironment of solid tumours may represent a therapeutic strategy for the inhibition of cancer progression.
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