Wang Chao, Ren Chuanfu, Hu Qiongyuan, Shen Xiaofei, Wang Meng, Yang Zhi, Xu En, Wang Xingzhou, Li Zijian, Yu Heng, Feng Qingzhao, Zhang Liang, Xia Xuefeng, Liu Song, Guan Wenxian
Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China.
Department of General Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing 210008, China.
J Cancer. 2022 Jan 4;13(4):1073-1085. doi: 10.7150/jca.68403. eCollection 2022.
Histidine-rich calcium binding protein (HRC) is a new type of Ca 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 inhibited migration, invasion, and proliferation of GC cell lines , while overexpression promoted GC cell migration, invasion, and proliferation , as well as the growth of subcutaneous tumors and peritoneal tumors . In terms of the mechanism, knockdown of 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 Ca/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.
富含组氨酸的钙结合蛋白（HRC）是一种新型的钙稳态调节剂，在调节细胞内钙稳态中发挥着不可忽视的作用。在此，我们证明HRC在人胃癌（GC）样本中表达上调，其表达水平与GC患者的总生存率（OS）以及GC细胞系的恶性潜能密切相关。敲低HRC可抑制GC细胞系的迁移、侵袭和增殖，而HRC过表达则促进GC细胞迁移、侵袭和增殖，以及皮下肿瘤和腹膜肿瘤的生长。在机制方面，敲低HRC可降低细胞内钙离子水平和钙调蛋白（CaM）水平。通过细胞功能实验，我们发现HRC通过Ca/CaM信号传导调节Raf/MEK/ERK途径，最终影响GC的上皮-间质转化（EMT）。综上所述，我们揭示了HRC是GC治疗的一个潜在靶点。
