A novel regulator of ER Ca2+ drives Hippo-mediated tumorigenesis
Menée sur des drosophiles, cette étude met en évidence le rôle de la protéine transmembranaire Emei dans la régulation de la concentration calcique du réticulum endoplasmique et la tumorigenèse liée à la voie de signalisation Hippo
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.