A novel regulator of ER Ca2+ drives Hippo-mediated tumorigenesis
| Autor: | Xianjue Ma, Aurelio A. Teleman, Jinan Fang, Peng Liu, Yue Qiu, Alexandra Moraru, Tian Xu, Jin Yu Lu |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research Hippo signaling pathway Cell growth Regulator Biology medicine.disease_cause Cell biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Hippo signaling 030220 oncology & carcinogenesis Second messenger system Genetics medicine Signal transduction Carcinogenesis Molecular Biology Intracellular |
| Zdroj: | Oncogene. 39:1378-1387 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/s41388-019-1076-z |
| Popis: | Calcium ion (Ca2+) is a versatile second messenger that regulates various cellular and physiological functions. However, the in vivo molecular mechanisms by which Ca2+ alterations contribute to tumor growth remain poorly explored. Here we show that Emei is a novel ER Ca2+ regulator that synergizes with RasV12 to induce tumor growth via JNK-mediated Hippo signaling. Emei disruption reduces ER Ca2+ level and subsequently leads to JNK activation and Hippo inactivation. Importantly, genetically increasing cytosolic Ca2+ concentration cooperates with RasV12 to drive tumor growth via inactivating the Hippo pathway. Finally, we identify POSH as a crucial link that bridges cytosolic Ca2+ alteration with JNK activation and Hippo-mediated tumor growth. Together, our findings provide a novel mechanism of tumor growth that acts through intracellular Ca2+ levels to modulate JNK-mediated Hippo signaling. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink