論文 - 詳細
| RRC ID | 58859 |
|---|---|
| 著者 | An L, Nie P, Chen M, Tang Y, Zhang H, Guan J, Cao Z, Hou C, Wang W, Zhao Y, Xu H, Jiao S, Zhou Z. |
| タイトル | MST4 kinase suppresses gastric tumorigenesis by limiting YAP activation via a non-canonical pathway. |
| ジャーナル | J Exp Med |
| Abstract |
Hyperactivation of YAP has been commonly associated with tumorigenesis, and emerging evidence hints at multilayered Hippo-independent regulations of YAP. In this study, we identified a new MST4-YAP axis, which acts as a noncanonical Hippo signaling pathway that limits stress-induced YAP activation. MST4 kinase directly phosphorylated YAP at Thr83 to block its binding with importin α, therefore leading to YAP cytoplasmic retention and inactivation. Due to a consequential interplay between MST4-mediated YAP phospho-Thr83 signaling and the classical YAP phospho-Ser127 signaling, the phosphorylation level of YAP at Thr83 was correlated to that at Ser127. Mutation of T83E mimicking MST4-mediated alternative signaling restrained the activity of both wild-type YAP and its S127A mutant mimicking loss of classical Hippo signal. Depletion of MST4 in mice promoted gastric tumorigenesis with diminished Thr83 phosphorylation and hyperactivation of YAP. Moreover, loss of MST4-YAP signaling was associated with poor prognosis of human gastric cancer. Collectively, our study uncovered a noncanonical MST4-YAP signaling axis essential for suppressing gastric tumorigenesis. |
| 巻・号 | 217(6) |
| 公開日 | 2020-6-1 |
| DOI | 10.1084/jem.20191817 |
| PII | 151647 |
| PMID | 32271880 |
| PMC | PMC7971137 |
| MeSH | Active Transport, Cell Nucleus Adaptor Proteins, Signal Transducing / chemistry Adaptor Proteins, Signal Transducing / metabolism* Amino Acid Sequence Carcinogenesis / metabolism* Carcinogenesis / pathology* Cell Line, Tumor Cell Nucleus / metabolism Cell Proliferation Culture Media, Serum-Free Female HEK293 Cells Humans Male Middle Aged Phosphorylation Phosphothreonine / metabolism Protein Binding Protein Serine-Threonine Kinases / deficiency Protein Serine-Threonine Kinases / metabolism* Signal Transduction* Stomach Neoplasms / enzymology* Stomach Neoplasms / pathology* Stress, Physiological Transcription Factors / chemistry Transcription Factors / metabolism* Treatment Outcome Tumor Suppressor Proteins / metabolism YAP-Signaling Proteins |
| IF | 10.892 |
| 引用数 | 1 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 10 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | GSS(RCB2277) GSU(RCB2278) |