Bibliographic Details
| Title: |
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) |
| Publisher Information: |
Nature Portfolio, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Science |
| Subject Terms: |
Science |
| More Details: |
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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2041-1723 |
| Relation: |
https://doaj.org/toc/2041-1723 |
| DOI: |
10.1038/s41467-024-54480-y |
| Access URL: |
https://doaj.org/article/89f00fc054b942f488db7155580cbccc |
| Accession Number: |
edsdoj.89f00fc054b942f488db7155580cbccc |
| Database: |
Directory of Open Access Journals |
