Somatic mutations in CCK2R alter receptor activity that promote oncogenic phenotypes.

Willard MD, Lajiness ME, Wulur IH, Feng B, Swearingen ML, Uhlik MT, Kinzler KW, Velculescu VE, Sjöblom T, Markowitz SD, Powell SM, Vogelstein B, Barber TD.
Source: Mol Cancer Res
Publication Date: (2012)
Issue: 10(6): 739-49
Cells used in publication:
Adipose stem cell, human normal
Species: human
Tissue Origin: adipose
Endothelial, colony forming, human(ECFC)
Species: human
Tissue Origin: extra-embryonic


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.