A novel regulator of ER Ca2+ drives Hippo-mediated tumorigenesis

• Verfasst von: Ma, Xianjue [VerfasserIn]
• Verfasst von: Lu, Jin-Yu [VerfasserIn]
• Verfasst von: Moraru, Alexandra [VerfasserIn]
• Verfasst von: Teleman, Aurelio A. [VerfasserIn]
• Verfasst von: Fang, Jinan [VerfasserIn]
• Verfasst von: Qiu, Yue [VerfasserIn]
• Verfasst von: Liu, Peng [VerfasserIn]
• Verfasst von: Xu, Tian [VerfasserIn]
• Titel: A novel regulator of ER Ca2+ drives Hippo-mediated tumorigenesis
• Verf.angabe: Xianjue Ma, Jin-Yu Lu, Alexandra Moraru, Aurelio A. Teleman, Jinan Fang, Yue Qiu, Peng Liu, Tian Xu
• Jahr: 2020
• Jahr des Originals: 2019
• Umfang: 10 S.
• Fussnoten: Published online: 24 October 2019 ; Im Titel ist "2+" hochgestellt ; Gesehen am 24.06.2020
• Titel Quelle: Enthalten in: Oncogene
• Ort Quelle: London : Springer Nature, 1997
• Jahr Quelle: 2020
• Band/Heft Quelle: 39(2020), 6, Seite 1378-1387
• ISSN Quelle: 1476-5594
• DOI: doi:10.1038/s41388-019-1076-z
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1702053970

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.