Recently, the team of Prof. Gao Peng from the Department of Pathology, School of Basic Medical Science, published a paper titled "CAP2 promotes gastric cancer metastasis by mediating the interaction between tumor cells and tumor-associated macrophages" in the Journal of Clinical Investigation, a classic journal of clinical medicine (District 1, Chinese Academy of Sciences, 5-year IF: 16.7), to reveal a new mechanism of gastric cancer cell crosstalk with tumor-associated macrophages. Zhang Guohao, doctoral student at the School of Basic Medical Science, is the first author, and Professor Gao Peng is the corresponding author. Shandong University is the first author unit and the only corresponding author unit.

Gastric cancer (GC) is the fifth most common cancer worldwide, with a high mortality rate among patients. The metastasis of cancer cells is the main cause of death for patients with GC. Mounting evidence has demonstrated the vital importance of tumor-associated macrophages in promoting tumor invasion and metastasis; however, the interaction between tumor cells and macrophages in GC is largely unknown. In this study, the team demonstrated that cyclase-associated protein 2 (CAP2) was upregulated in GC, especially in cases with lymph node metastasis, and was correlated with a poorer prognosis. The transcription factor JUN is directly bound to the promoter region of CAP2 and activates CAP2 transcription. The N-terminal domain of CAP2 is bound to the WD5-7 domain of receptor for activated C kinase 1 (RACK1) and induced M2 macrophage polarization by activating the SRC/focal adhesion kinase (FAK)/ ERK signaling pathway, which resulted in interleukin-4 (IL4) and IL10 secretion. Polarized M2 macrophages formed a positive feedback loop of TGFB1/JUN/CAP2 by secreting transforming growth factor β (TGFB1), which continuously activated CAP2 expression. Furthermore, this study identified Salvianolic acid B as an inhibitor of CAP2, which effectively inhibited GC cell invasion and metastasis by suppressing the above signaling pathway. It was revealed that CAP2, a key molecule mediating the interaction between GC cells and tumor-associated macrophages, may be a promising therapeutic target for suppressing tumor metastasis in GC.

Professor Gao Peng's research team has been committed to the study of tumor gene changes and expression regulation. In recent years, related papers have been published in the Journal of Clinical Investigation, Cancer Research, Journal of Pathology, Journal of Hepatology, Molecular Cancer, Cell Death & Differentiation and other journals. This research was supported by the National Natural Science Foundation of China and the Taishan Scholar Distinguished Professor Program.