APC/C是在细胞周期调控中发挥关键作用的E3泛素连接酶复合体。其中， APC2是APC/C的催化核心蛋白。最近，本课题组建立了Apc2髓细胞条件性敲除小鼠，发现Apc2敲除小鼠可以抵抗自发肿瘤、排斥移植肿瘤、抑制AOM-DSS诱导肠癌的发生，提示缺失Apc2的髓细胞具有强烈的抗肿瘤活性。另一方面，肿瘤相关巨噬细胞的大量浸润在肿瘤发生发展中的重要作用正日益受到重视。我们进一步发现， Apc2敲除的巨噬细胞表现M1型基因表达上升、M2型基因表达下降的现象，提示APC2在巨噬细胞M1/M2型极化中发挥重要作用。本课题将在这些研究工作的基础上，进一步明确髓细胞APC2在肿瘤发生及巨噬细胞M1/M2型极化中的作用，深入探索APC2影响巨噬细胞极化的分子机制及其在肿瘤发生中的作用。这些研究可望揭示APC2在肿瘤发生与巨噬细胞极化中的作用，为肿瘤的早期诊断、预防及相关肿瘤的免疫治疗提供新的实验证据。

APC2 is a catalytic core subunit of APC/C (anaphase promoting complex/cyclosome), which is a multi-subunit E3 ubiquitin ligase that primarily governs cell cycle progression. Recently, myeloid cell-specific knockout mice of Apc2 gene was generated in our laboratory and the mutant mice could repress spontaneous tumor, eliminate subcutaneous tumor isografts, and restrain AOM-DSS-induced colon tumor, which suggest that myeloid cells that specific knockout Apc2 gene have energetic antitumoral activities. On the other hand, the roles of tumor-associated macrophages (TAM) in tumorigenesis and tumor progression are attracting attentions. Furthermore, we found that Apc2 knockout macrophages express elevated level of M1 characteristic genes and decreased M2 featured genes, which indicates APC2 might contribute to macrophage polarization. Based on these primary data, we propose to determine the roles of myeloid APC2 in tumorigenesis and polarization of macrophages, to explore the molecular mechanisms that how APC2 orchestrating the polarization of macrophages and its potential functions in tumorigenesis. Our research will disclose the influence of APC2 in the correlation between macrophage polarization and tumorigenesis and shed new insights on theoretical basis on the early prognosis, prevention and immunotherapy of related cancer.