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Functional annotation of the Hippo pathway somatic mutations in human cancers

Authors :
Han Han
Zhen Huang
Congsheng Xu
Gayoung Seo
Jeongmin An
Bing Yang
Yuhan Liu
Tian Lan
Jiachen Yan
Shanshan Ren
Yue Xu
Di Xiao
Jonathan K. Yan
Claire Ahn
Dmitry A. Fishman
Zhipeng Meng
Kun-Liang Guan
Ruxi Qi
Ray Luo
Wenqi Wang
Source :
Nature Communications, Vol 15, Iss 1, Pp 1-18 (2024)
Publication Year :
2024
Publisher :
Nature Portfolio, 2024.

Abstract

Abstract The Hippo pathway is commonly altered in cancer initiation and progression; however, exactly how this pathway becomes dysregulated to promote human cancer development remains unclear. Here we analyze the Hippo somatic mutations in the human cancer genome and functionally annotate their roles in targeting the Hippo pathway. We identify a total of 85 loss-of-function (LOF) missense mutations for Hippo pathway genes and elucidate their underlying mechanisms. Interestingly, we reveal zinc-finger domain as an integral structure for MOB1 function, whose LOF mutations in head and neck cancer promote tumor growth. Moreover, the schwannoma/meningioma-derived NF2 LOF mutations not only inhibit its tumor suppressive function in the Hippo pathway, but also gain an oncogenic role for NF2 by activating the VANGL-JNK pathway. Collectively, our study not only offers a rich somatic mutation resource for investigating the Hippo pathway in human cancers, but also provides a molecular basis for Hippo-based cancer therapy.

Subjects

Subjects :
Science

Details

Language :
English
ISSN :
20411723
Volume :
15
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Nature Communications
Publication Type :
Academic Journal
Accession number :
edsdoj.89f00fc054b942f488db7155580cbccc
Document Type :
article
Full Text :
https://doi.org/10.1038/s41467-024-54480-y