The metabolic/pH sensor soluble adenylyl cyclase is a tumor suppressor protein
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Lavoisier Ramos-Espiritu1, Ana Diaz1,2, Charlee Nardin2,3, Anthony J. Saviola1,2, Fiona Shaw2, Tamar Plitt4, Xia Yang4, Jedd Wolchok4,5, Edyta C. Pirog6, Garrett Desman7, Andrea Sboner6,8, Tuo Zhang9, Jenny Xiang9, Taha Merghoub4,5, Lonny R. Levin1, Jochen Buck1, Jonathan H. Zippin2,10
1Department of Pharmacology, Weill Cornell Medical College, New York, NY, USA
2Department of Dermatology, Weill Cornell Medical College, New York, NY, USA
3Service de Dermatologie, Centre Hospitalier Universitaire, Besançon, France
4Ludwig Collaborative and Swim Across America Lab, Memorial Sloan Kettering Cancer Center, New York, NY, USA
5Department of Medicine and Ludwig Center, Memorial Sloan Kettering Cancer Center, New York, NY, USA
6Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA
7Department of Pathology and Laboratory Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
8The Institute for Computational Biomedicine, Weill Cornell Medical College, New York, NY, USA
9Genomics Resources Core Facility, Weill Cornell Medical College, New York, NY, USA
10Meyer Cancer Center, Weill Cornell Medical College, New York, NY, USA
Jonathan H. Zippin, email: email@example.com
Keywords: sAC, cAMP, tumor suppressor, microdomain, metabolic sensor
Received: January 15, 2016 Accepted: June 01, 2016 Published: June 15, 2016
cAMP signaling pathways can both stimulate and inhibit the development of cancer; however, the sources of cAMP important for tumorigenesis remain poorly understood. Soluble adenylyl cyclase (sAC) is a non-canonical, evolutionarily conserved, nutrient- and pH-sensing source of cAMP. sAC has been implicated in the metastatic potential of certain cancers, and it is differentially localized in human cancers as compared to benign tissues. We now show that sAC expression is reduced in many human cancers. Loss of sAC increases cellular transformation in vitro and malignant progression in vivo. These data identify the metabolic/pH sensor soluble adenylyl cyclase as a previously unappreciated tumor suppressor protein.
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