ZBTB28 inhibits breast cancer by activating IFNAR and dual blocking CD24 and CD47 to enhance macrophages phagocytosis
ZBTB28 inhibits breast cancer by activating IFNAR and dual blocking CD24 and CD47 to enhance macrophages phagocytosis
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ZBTB28通过激活IFNAR并双重阻断CD24和CD47增强巨噬细胞吞噬作用抑制乳腺癌
DOI：
10.1007/s00018-021-04124-x
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发表时间：
2022-02-01
影响因子：
8
通讯作者：
Xiang, Tingxiu
中科院分区：
文献类型：
--
作者：
Li, Li;Gong, Yijia;Xiang, Tingxiu
乳腺癌是女性癌症死亡的主要原因。到目前为止，晚期乳腺癌仍然缺乏有效的治疗策略和可靠的预后指标。本文就肿瘤抑制基因ZBTB28在乳腺癌中的生理病理功能及其调控机制作一综述。由于启动子CpG甲基化，ZBTB28在乳腺癌中经常沉默，其表达与乳腺癌患者生存率呈正相关。通过细胞增殖、凋亡、细胞周期、上皮间充质转化（epithelial mesenchymal transition， EMT）和异种移植物生长等一系列体外和体内实验，阐明了ZBTB28在乳腺癌中的抗肿瘤作用。ZBTB28可直接调控IFNAR激活干扰素刺激基因，增强巨噬细胞活化。ZBTB28在乳腺癌细胞中的异位表达足以下调CD24和CD47，促进巨噬细胞的吞噬作用，表明ZBTB28有利于抗CD24和抗CD47联合治疗。总之，我们的研究结果揭示了ZBTB28作为肿瘤抑制基因的作用模式，并表明ZBTB28是乳腺癌巨噬细胞吞噬的重要调节因子，有望为乳腺癌患者开发新的治疗策略。
Breast cancer is the leading cause of cancer death in female. Until now, advanced breast cancer is still lack effective treatment strategies and reliable prognostic markers. In the present article, we introduced the physiologic and pathologic functions and regulation mechanisms of ZBTB28, a tumor suppressor gene, in breast cancer. ZBTB28 is frequently silenced in breast cancer due to promoter CpG methylation, and its expression is positively correlated with breast cancer patient survival. The antineoplastic effect of ZBTB28 in breast cancer was elucidated through a series of in vitro and in vivo measurements, including cell proliferation, apoptosis, cell cycle, epithelial mesenchymal transition (EMT), and growth of xenografts. Furthermore, ZBTB28 can directly regulate IFNAR to activate interferon-stimulated genes and potentiate macrophage activation. Ectopic ZBTB28 expression in breast cancer cells was sufficient to downregulate CD24 and CD47 to promote phagocytosis of macrophages, demonstrating that ZBTB28 was beneficial for the combination treatment of anti-CD24 and anti-CD47. Collectively, our results reveal a mode of action of ZBTB28 as a tumor suppressor gene and suggest that ZBTB28 is an important regulator of macrophage phagocytosis in breast cancer, holding promise for the development of novel therapy strategies for breast cancer patients.