CD47 promotes T-cell lymphoma metastasis by up-regulating AKAP13-mediated RhoA activation
CD47 promotes T-cell lymphoma metastasis by up-regulating AKAP13-mediated RhoA activation
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CD47 通过上调 AKAP13 介导的 RhoA 激活促进 T 细胞淋巴瘤转移
DOI：
10.1093/intimm/dxab002
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发表时间：
2021
影响因子：
4.4
通讯作者：
Matsuda Tadashi
中科院分区：
文献类型：
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作者：
Kitai Yuichi;Ishiura Marie;Saitoh Kodai;Matsumoto Naoki;Owashi Kimiya;Yamada Shunsuke;Muromoto Ryuta;Kashiwakura Jun-ichi;Oritani Kenji;Matsuda Tadashi
CD 47是一种50 kDa的跨膜蛋白，促进整合素介导的细胞粘附并抑制吞噬细胞的细胞吞噬。由于CD 47阻断促进巨噬细胞吞噬癌细胞，因此重要的是阐明CD 47信号传导的机制，以便开发涉及CD 47过表达癌细胞的疾病的治疗方法，包括乳腺癌和淋巴瘤。在这里，我们表明，CD 47起着至关重要的作用，在T细胞淋巴瘤转移上调基础RhoA活性独立于其抗吞噬功能。CD 47与AKAP 13（RhoA特异性鸟嘌呤核苷酸交换因子（GEF））相互作用，促进AKAP 13介导的RhoA活化。我们的研究表明，CD 47在AKAP 13-RhoA轴上具有新的功能，并表明CD 47-AKAP 13相互作用将成为T细胞淋巴瘤治疗的新靶点。
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.