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Weight-bearing activity impairs nuclear membrane and genome integrity via YAP activation in plantar melanoma

Authors
 Jimyung Seo  ;  HyunSeok Kim  ;  Kyoung Il Min  ;  Changgon Kim  ;  Yongsoo Kwon  ;  Zhenlong Zheng  ;  Yusung Kim  ;  Hyung-Soon Park  ;  Young Seok Ju  ;  Mi Ryung Roh  ;  Kee Yang Chung  ;  Joon Kim 
Citation
 NATURE COMMUNICATIONS, Vol.13(1) : 2214, 2022-04 
Journal Title
NATURE COMMUNICATIONS
Issue Date
2022-04
MeSH
Humans ; Melanoma* / genetics ; Melanoma* / pathology ; Nuclear Envelope / pathology ; Skin Neoplasms* / genetics ; Skin Neoplasms* / pathology ; Weight-Bearing / physiology
Abstract
Acral melanoma commonly occurs in areas that are not exposed to much sunlight, such as the sole of the foot. Little is known about risk factors and mutational processes of plantar acral melanoma. Nuclear envelope rupture during interphase contributes to genome instability in cancer. Here, we show that the nuclear and micronuclear membranes of melanoma cells are frequently ruptured by macroscopic mechanical stress on the plantar surface due to weight-bearing activities. The marginal region of plantar melanoma nodules exhibits increased nuclear morphological abnormalities and collagen accumulations, and is more susceptible to mechanical stress than the tumor center. An increase in DNA damage coincides with nuclear membrane rupture in the tumor margin. Nuclear envelope integrity is compromised by the mechanosensitive transcriptional cofactor YAP activated in the tumor margin. Our results suggest a mutagenesis mechanism in melanoma and explain why plantar acral melanoma is frequent at higher mechanical stress points.
Files in This Item:
T202204731.pdf Download
DOI
10.1038/s41467-022-29925-x
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
Yonsei Authors
Roh, Mi Ryung(노미령) ORCID logo https://orcid.org/0000-0002-6285-2490
Chung, Kee Yang(정기양) ORCID logo https://orcid.org/0000-0003-3257-0297
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/191367
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