“炎-癌”相互作用参与结肠癌发生发展全过程。虽研究多年，但机制不清。原因之一是种类繁多的炎性细胞（如肿瘤相关巨噬细胞和肿瘤相关中性粒细胞等）与癌细胞间作用纷繁复杂。要全面理解“炎-癌”的密切关系需深入解析每种炎性细胞与癌细胞相互作用机理。我们前期研究发现一种肿瘤相关巨噬细胞（TAM）和癌细胞之间的新型双向联系：TAM释放炎症因子PGE2正向调控结肠癌细胞的表观调节蛋白UHRF1，而癌细胞UHRF1反馈性促进TAM产生更多PGE2，形成“TAM炎症因子-癌细胞表观调节因子-TAM炎症因子”的正反馈环路，驱动肿瘤发展。基于此，本项目旨在探讨该环路的分子组成，明确环路核心基因UHRF1促癌作用的分子基础，揭示TAM与结肠癌细胞双向联系、相互协助的促癌新机理，为阻断该环路、抑癌治疗提供新靶点。

Mechanistically, inflammatory cells (such as tumor-associated macrophages and neutrophils) are known to be involved in the entirety of colon cancer pathogenesis. Although the research topic on the interactions between inflammation and cancer cells has been intensively studied for many years, the detailed mechanisms underlying their interactions are still unclear, in part due to the complexity of interwoven and countless cross-talks among various types of inflammation cells and colon cancer cells within tumor microenvironment. To fully understand the mechanisms of colon cancer development, it is necessary to deepen our understanding of how these cells mutually communicate with each other. Recently, we have found a new two-way cross-talk between tumor-associated macrophages (TAM) and colon cancer cells: TAM releases an inflammatory factor, PGE2, to upregulate an epigenetic regulator UHRF1 in colon cancer cells, while UHRF1-expressing colon cancer cells effectively promote TAM to produce more PGE2, thus forming a positive feedback loop of “TAM/inflammatory factor - colon cancer cells/ epigenetic regulator - TAM/inflammatory factor”. This loop acts to promote cancer development. In this study, we aim to unravel the molecular basis of this loop and identify the target genes that mediate UHRF1’s tumor-promoting effects. By doing so, we hope to reveal the mechanisms underlying this cross-talk and oncogenic cooperation between TAM and colon cancer cells towards providing new targets for blocking this circuit and designing novel cancer treatments.