Abstract
Gastric cancer is a common malignant tumour of gastrointestinal tract with high incidence and low early diagnosis rate. Surgery is its main treatment modality, but some patients have poor prognosis. The rise of immunotherapy provides a new therapeutic strategy for gastric cancer treatment. Elucidating the mechanism of action of immune cells in the tumour microenvironment is the cornerstone for developing new tumour immunotherapy strategies. Previous studies have found that Fra-1 is highly expressed in gastric cancer and is closely associated with macrophage polarisation. In order to further elucidate the specific mechanism, this study firstly used in vitro co-culture experiments to verify that the high expression of Fra-1 in gastric cancer cells induced macrophage M2 polarisation; then, whole proteomics combined with in vitro cellular experiments were used to clarify the specific mechanism by which Fra-1 induced macrophage M2 polarisation by regulating HMGA2 expression in gastric cancer cells. Finally, in vivo experiments further elucidated that Fra-1 induces macrophage polarisation in gastric cancer cells and participates in tumourigenesis and development. The aim of this study was to systematically elucidate the role of Fra-1 in the tumour microenvironment and its possible mechanisms, and to provide an experimental basis for the development of immunotherapeutic strategies for gastric cancer.