Abstract
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.
Original language | English (US) |
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Pages (from-to) | 1378-1387 |
Number of pages | 10 |
Journal | Oncogene |
Volume | 39 |
Issue number | 6 |
DOIs | |
State | Published - Feb 6 2020 |
Externally published | Yes |
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cancer Research