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. 2020 Mar 6;11:112.
doi: 10.3389/fendo.2020.00112. eCollection 2020.

Gastrin, Cholecystokinin, Signaling, and Biological Activities in Cellular Processes

Free PMC article

Gastrin, Cholecystokinin, Signaling, and Biological Activities in Cellular Processes

Qiang Zeng et al. Front Endocrinol (Lausanne). .
Free PMC article


The structurally-related peptides, gastrin and cholecystokinin (CCK), were originally discovered as humoral stimulants of gastric acid secretion and pancreatic enzyme release, respectively. With the aid of methodological advances in biochemistry, immunochemistry, and molecular biology in the past several decades, our concept of gastrin and CCK as simple gastrointestinal hormones has changed considerably. Extensive in vitro and in vivo studies have shown that gastrin and CCK play important roles in several cellular processes including maintenance of gastric mucosa and pancreatic islet integrity, neurogenesis, and neoplastic transformation. Indeed, gastrin and CCK, as well as their receptors, are expressed in a variety of tumor cell lines, animal models, and human samples, and might contribute to certain carcinogenesis. In this review, we will briefly introduce the gastrin and CCK system and highlight the effects of gastrin and CCK in the regulation of cell proliferation and apoptosis in both normal and abnormal conditions. The potential imaging and therapeutic use of these peptides and their derivatives are also summarized.

Keywords: CCK; G protein-coupled receptor; cancer; gastrin; imaging; therapeutics.


Figure 1
Figure 1
Proposed diagrams of gastrin- and CCK-induced signaling pathways through CCK2R and CCK1R in normal and tumor cells. In response to gastrin and CCK, CCK2R couples to Gq and Gα12/13 proteins to promote cell proliferation and inhibit apoptosis through activation of PLC/Ca2+/PKC, MAPK, p125fak, Src, and PI3K/AKT cascades, as well as transactivation of EGFR, whereas CCK1R couples to Gq and Gs to exhibit trophic effects through activation of PLC/Ca2+/PKC, AC/cAMP/PKA, MAPK, and PI3K/AKT pathways.

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