Calcr, short for calcitonin receptor, is a G-protein-coupled receptor crucial for maintaining calcium homeostasis [1,3,5]. It is involved in multiple biological processes, with its signaling pathways potentially interacting with various cellular functions [1,2,4]. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, are valuable tools for studying its functions.

In muscle satellite (stem) cells, CalcR-mutant KO mouse models have shown that the CalcR-PKA-Yap1 axis is critical for maintaining quiescence. Transgenic expression of the catalytic domain of protein kinase A (PKA) can restore quiescence in CalcR-mutant MuSCs, and genetic inactivation of Yap1 in these cells also reinstates quiescence [2].

In renal cell carcinoma (RCC), CALCR depletion in cell models inhibits cell proliferation and migration, induces apoptosis and cycle arrest, and is essential for in vivo tumor formation. Mechanistically, CALCR binds to CD44, stabilizing it [1].

In non-small-cell lung cancer (NSCLC), CALCR knockdown suppresses cell proliferation, migration, enhances apoptosis and arrests cell cycle, verified by in vivo mouse xenograft models [3].

In liver cancer, high CALCR expression is associated with shortened survival, and in vitro, si-CALCR increases apoptosis while reducing proliferation and migration in HepG-2 and HuH-7 cells [5].

In gastric cancer, CALCR knockdown in cell lines and nude mouse models reduces proliferation, increases apoptosis, and inhibits migration and invasion, and it interacts with ANTXR1 [6].

In conclusion, Calcr plays diverse and essential biological functions in maintaining stem cell quiescence and is significantly involved in the progression of multiple cancers including RCC, NSCLC, liver cancer, and gastric cancer. The use of KO/CKO mouse models and other in vivo studies has been instrumental in revealing these functions, providing potential therapeutic targets for cancer treatment.