A nuclear cAMP microdomain suppresses tumor growth by Hippo pathway inactivation

• DOI: 10.1016/j.celrep.2022.111412
• Publication Date: 2022-09-27T14:34:10Z
• Authors: Marek M. Drozdz; Ashley S. Doane; Rached Alkallas; Garrett Desman; Rohan Bareja; Michael Reilly; Jakyung Bang; Maftuna Yusupova; Jaewon You; Zuhal Eraslan; Jenny Z. Wang; Akanksha Verma; Kelsey Aguirre; Elsbeth Kane; Ian R. Watson; Olivier Elemento; Elena Piskounova; Taha Merghoub; Jonathan H. Zippin
• Keywords: Lipid microdomain; Hippo signaling pathway

Cyclic AMP (cAMP) signaling is localized to multiple spatially distinct microdomains, but the role of cAMP microdomains in cancer cell biology poorly understood. Here, we present a tunable genetic system that allows us activate specific microdomains. We uncover nuclear microdomain activates tumor-suppressive pathway broad range cancers by inhibiting YAP, key effector protein Hippo pathway, inside nucleus. show induces LATS-dependent leading phosphorylation YAP solely at serine 397 and export from nucleus with no change stability. Thus, inhibition other known mechanisms regulation. Pharmacologic targeting remains an untapped therapeutic approach for cancer; thus, drugs directed may provide avenues treatment cancer.