Oncotarget

Research Papers:

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 and Jonathan H. Zippin _

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Oncotarget. 2016; 7:45597-45607. https://doi.org/10.18632/oncotarget.10056

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Abstract

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

Correspondence to:

Jonathan H. Zippin, email: [email protected]

Keywords: sAC, cAMP, tumor suppressor, microdomain, metabolic sensor

Received: January 15, 2016     Accepted: June 01, 2016     Published: June 15, 2016

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.


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