Takahashi Shinichiro
Division of Laboratory Medicine, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Miyagino-ku, Sendai 983-8536, Japan.
Biomed Rep. 2018 Jul;9(1):3-7. doi: 10.3892/br.2018.1102. Epub 2018 May 23.
Signal regulatory protein α (SIRPα), also known as cluster of differentiation (CD)172a or Src homology 2 domain-containing phosphatase substrate-1, is a cell surface receptor expressed on myeloid and hematopoietic stem cells and neurons. Accumulating data suggests an important role of SIRPα in cell signaling as a negative regulator of the phosphatidylinositol 3-kinase signaling and mitogen-activated protein kinase pathways. In various cancers, including prostate, breast and liver, as well as astrocytoma and myeloid malignancies, downregulation of SIRPα is frequently observed, resulting in activation of these downstream signaling pathways. In turn, cell proliferation, transformation, migration and invasion may occur. Recently, it has been reported that blocking CD47, an anti-phagocytic signal expressed on tumor cells and an SIRPα ligand, may serve as a promising therapeutic approach, particular for the treatment of acute myeloid leukemia. In the present review, the current findings on SIRPα are summarized, with particular focus on its role in cancer.
信号调节蛋白α（SIRPα），也称为分化簇（CD）172a或含Src同源2结构域的磷酸酶底物-1，是一种在髓系细胞、造血干细胞和神经元上表达的细胞表面受体。越来越多的数据表明，SIRPα作为磷脂酰肌醇3激酶信号传导和丝裂原活化蛋白激酶途径的负调节因子，在细胞信号传导中发挥重要作用。在包括前列腺癌、乳腺癌和肝癌以及星形细胞瘤和髓系恶性肿瘤在内的各种癌症中，经常观察到SIRPα的下调，从而导致这些下游信号通路的激活。进而可能发生细胞增殖、转化、迁移和侵袭。最近，有报道称，阻断肿瘤细胞上表达的抗吞噬信号CD47（一种SIRPα配体）可能是一种有前景的治疗方法，特别是对于急性髓系白血病的治疗。在本综述中，总结了关于SIRPα的当前研究结果，特别关注其在癌症中的作用。
