Journal
ONCOTARGET
Volume 7, Issue 29, Pages 45597-45607Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.10056
Keywords
sAC; cAMP; tumor suppressor; microdomain; metabolic sensor
Categories
Funding
- Universite de Franche Comte Sciences Medicales et Pharmaceutiques - Annee-Recherche
- Societe Francaise de Dermatologie - AO bourse de soutien pour la formation a la recherche en dermatologie
- College des Enseignants de Dermatologie En France - Bourse CEDEF d'aide a la mobilite
- Melanoma Research Alliance Team Science Award
- American Skin Association
- National Cancer Institute (NCI) [NIH T32 CA062948, K08 CA 160657-01]
- Swim Across America
- Ludwig Cancer Research
- Annenberg-Hazen Foundation
- Clinique Clinical Scholars Award
- [GM107442]
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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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