{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The cholecystokinin B receptor (CCKBR), also known as the CCK2 receptor, plays multifaceted roles that depend on the tissue context. In the brain, for example, stress‐induced upregulation of CCKBR within the medial prefrontal cortex has been shown to contribute to anxiety‐ and depression–like behaviors; blockade of this receptor produces a resilient phenotype."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In the gastrointestinal system, CCKBR acts as a critical mediator of gastrin/progastrin signaling. It is expressed on a distinct population of gastric (+4) stem cells that can be activated and expanded by progastrin, thereby promoting gland fission and facilitating carcinogenic processes in the stomach."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In both gastric and colorectal cancers, tumor‐suppressive microRNAs (such as miR-148a and miR-148b) can target CCKBR, leading to reduced cell proliferation and migration in a gastrin-dependent manner"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Similarly, in pancreatic cancer, miR-148a suppresses tumor growth by downregulating CCKBR"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", while in colorectal carcinoma gastrin acting via the wild-type receptor induces apoptosis through modulation of NF-κB and other downstream targets."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In addition, studies investigating the neurobiology of panic and other stress-related disorders have implicated CCKBR as one of the candidate genes whose dysregulation—via modulation by specific microRNAs—may contribute to pathological anxiety responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Furthermore, in animal models, genetic inactivation of CCKBR leads to disrupted satiety signaling, manifesting as hyperphagia and obesity, which underscores its role in the central regulation of food intake."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Finally, the receptor mediates gastrin-induced migration of gastric cancer cells via activation of MAPK cascades, highlighting its contribution to cancer cell motility."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Collectively, these findings indicate that CCKBR is a pivotal receptor that integrates hormonal, neural, and molecular signals to modulate mood, regulate stem cell activity, and influence tumorigenesis across a spectrum of tissues.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Vincent Vialou, Rosemary C Bagot, Michael E Cahill, et al. 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