The metabolic/pH sensor soluble adenylyl cyclase is a tumor suppressor protein.
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.
Department of Pharmacology, Weill Cornell Medical College, New York, NY, USA.
Lavoisier
L
Ramos-Espiritu
Department of Pharmacology, Weill Cornell Medical College, New York, NY, USA.|Department of Dermatology, Weill Cornell Medical College, New York, NY, USA.
Ana
A
Diaz
Department of Dermatology, Weill Cornell Medical College, New York, NY, USA.|Service de Dermatologie, Centre Hospitalier Universitaire, Besançon, France.
Charlee
C
Nardin
Department of Pharmacology, Weill Cornell Medical College, New York, NY, USA.|Department of Dermatology, Weill Cornell Medical College, New York, NY, USA.
Anthony J
AJ
Saviola
Department of Dermatology, Weill Cornell Medical College, New York, NY, USA.
Fiona
F
Shaw
Ludwig Collaborative and Swim Across America Lab, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Tamar
T
Plitt
Ludwig Collaborative and Swim Across America Lab, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Xia
X
Yang
Ludwig Collaborative and Swim Across America Lab, Memorial Sloan Kettering Cancer Center, New York, NY, USA.|Department of Medicine and Ludwig Center, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Jedd
J
Wolchok
Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA.
Edyta C
EC
Pirog
Department of Pathology and Laboratory Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Garrett
G
Desman
Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA.|The Institute for Computational Biomedicine, Weill Cornell Medical College, New York, NY, USA.
Andrea
A
Sboner
Genomics Resources Core Facility, Weill Cornell Medical College, New York, NY, USA.
Tuo
T
Zhang
Genomics Resources Core Facility, Weill Cornell Medical College, New York, NY, USA.
Jenny
J
Xiang
Ludwig Collaborative and Swim Across America Lab, Memorial Sloan Kettering Cancer Center, New York, NY, USA.|Department of Medicine and Ludwig Center, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Taha
T
Merghoub
Department of Pharmacology, Weill Cornell Medical College, New York, NY, USA.
Lonny R
LR
Levin
Department of Pharmacology, Weill Cornell Medical College, New York, NY, USA.
Jochen
J
Buck
Department of Dermatology, Weill Cornell Medical College, New York, NY, USA.|Meyer Cancer Center, Weill Cornell Medical College, New York, NY, USA.
Jonathan H
JH
Zippin
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009369:Neoplasms / Q000201:enzymology*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D025521:Tumor Suppressor Proteins; D000262:Adenylyl Cyclases
cAMP; metabolic sensor; microdomain; sAC; tumor suppressor