1. Somatic mutations in CCK2R alter receptor activity that promote oncogenic phenotypes
- Author
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Michelle L. Swearingen, Kenneth W. Kinzler, Melinda D. Willard, Bert Vogelstein, Mark T. Uhlik, Victor E. Velculescu, Thomas D. Barber, Tobias Sjöblom, Sanford D. Markowitz, Steven M. Powell, Mary E. Lajiness, Bo Feng, and Isabella H. Wulur
- Subjects
Vascular Endothelial Growth Factor A ,Cancer Research ,Angiogenesis ,Somatic cell ,DNA Mutational Analysis ,Immunoblotting ,Neovascularization, Physiologic ,Biology ,medicine.disease_cause ,Transfection ,Article ,Mice ,RNA interference ,Cell Movement ,Stomach Neoplasms ,medicine ,Animals ,Humans ,Receptor ,Molecular Biology ,Cell Shape ,Cells, Cultured ,Mutation ,Neovascularization, Pathologic ,Endothelial Cells ,Phenotype ,Coculture Techniques ,Receptor, Cholecystokinin B ,Cell Transformation, Neoplastic ,HEK293 Cells ,Oncology ,Microscopy, Fluorescence ,Cholecystokinin B receptor ,Cancer research ,NIH 3T3 Cells ,RNA Interference ,Carcinogenesis ,Colorectal Neoplasms - Abstract
The roles of cholecystokinin 2 receptor (CCK2R) in numerous physiologic processes in the gastrointestinal tract and central nervous system are well documented. There has been some evidence that CCK2R alterations play a role in cancers, but the functional significance of these alterations for tumorigenesis is unknown. We have identified six mutations in CCK2R among a panel of 140 colorectal cancers and 44 gastric cancers. We show that these mutations increase receptor activity, activate multiple downstream signaling pathways, increase cell migration, and promote angiogenesis. Our findings suggest that somatic mutations in CCK2R may promote tumorigenesis through deregulated receptor activity and highlight the importance of evaluating CCK2R inhibitors to block both the normal and mutant forms of the receptor. Mol Cancer Res; 10(6); 739–49. ©2012 AACR.
- Published
- 2012