The metabolic/pH sensor soluble adenylyl cyclase is a tumor suppressor protein

Lavoisier Ramos-Espiritu, Ana Diaz, Charlee Nardin, Anthony J. Saviola, Fiona Shaw, Tamar Plitt, Xia Yang, Jedd Wolchok, Edyta C. Pirog, Garrett Desman, Andrea Sboner, Tuo Zhang, Jenny Xiang, Taha Merghoub, Lonny R. Levin, Jochen Buck, Jonathan H. Zippin

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)45597-45607
Number of pages11
JournalOncotarget
Volume7
Issue number29
DOIs
StatePublished - 2016

Keywords

  • CAMP
  • Metabolic sensor
  • Microdomain
  • Tumor suppressor
  • sAC

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