Histidine-rich calcium binding protein promotes gastric cancer cell proliferation, migration, invasion and epithelial-mesenchymal transition through Raf/MEK/ERK signaling

Histidine-rich calcium binding protein (HRC) is a new type of Ca2+ homeostasis regulator, which acts as a nonnegligible role in regulating intracellular calcium homeostasis. Here, we demonstrated that HRC expression was upregulated in human gastric cancer (GC) samples, and its expression level was closely correlated with the overall survival (OS) rate of GC patients and the malignant potential of GC cell lines. Knockdown of HRC inhibited migration, invasion, and proliferation of GC cell lines in vitro, while HRC overexpression promoted GC cell migration, invasion, and proliferation in vitro, as well as the growth of subcutaneous tumors and peritoneal tumors in vivo. In terms of the mechanism, knockdown of HRC reduced the intracellular calcium ion level and the CaM protein level. Through cell function experiments, we found that HRC regulated the Raf/MEK/ERK pathway through Ca2+/CaM signaling and ultimately affected the epithelial-mesenchyme transition (EMT) of GC. In summary, we revealed that HRC represents a potential target for GC treatment.