CD47 通过上调 AKAP13 介导的 RhoA 激活促进 T 细胞淋巴瘤转移。
CD47 promotes T-cell lymphoma metastasis by up-regulating AKAP13-mediated RhoA activation.
机构信息
Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-Ku, Sapporo, Hokkaido, Japan.
Department of Hematology, International University of Health and Welfare, Narita, Chiba, Japan.
出版信息
Int Immunol. 2021 Apr 22;33(5):273-280. doi: 10.1093/intimm/dxab002.
CD47, a 50 kDa transmembrane protein, facilitates integrin-mediated cell adhesion and inhibits cell engulfment by phagocytes. Since CD47 blocking promotes engulfment of cancer cells by macrophages, it is important to clarify the mechanism of CD47 signaling in order to develop treatments for diseases involving CD47-overexpressing cancer cells, including breast cancer and lymphoma. Here, we show that CD47 plays an essential role in T-cell lymphoma metastasis by up-regulating basal RhoA activity independent of its anti-phagocytic function. CD47 interacts with AKAP13, a RhoA-specific guanine nucleotide exchange factor (GEF), and facilitates AKAP13-mediated RhoA activation. Our study shows that CD47 has a novel function on the AKAP13-RhoA axis and suggests that CD47-AKAP13 interaction would be a novel target for T-cell lymphoma treatment.
CD47 是一种 50kDa 的跨膜蛋白，它促进整合素介导的细胞黏附，并抑制吞噬细胞吞噬细胞。由于 CD47 阻断促进了巨噬细胞对癌细胞的吞噬作用，因此阐明 CD47 信号通路的机制对于开发涉及 CD47 过表达癌细胞的疾病的治疗方法（包括乳腺癌和淋巴瘤）非常重要。在这里，我们表明 CD47 通过独立于其抗吞噬作用的功能而上调基础 RhoA 活性，在 T 细胞淋巴瘤转移中发挥重要作用。CD47 与 AKAP13 相互作用，AKAP13 是一种 RhoA 特异性鸟嘌呤核苷酸交换因子（GEF），并促进 AKAP13 介导的 RhoA 激活。我们的研究表明 CD47 在 AKAP13-RhoA 轴上具有新的功能，并表明 CD47-AKAP13 相互作用可能成为 T 细胞淋巴瘤治疗的新靶点。
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