CD47 is a ubiquitously expressed cell surface receptor, which is widely known for preventing macrophage-mediated phagocytosis by interacting with signal regulatory protein α (SIRPα) on the surface of macrophages. In addition to its role in phagocytosis, emerging studies have reported numerous noncanonical functions of CD47 that include regulation of various cellular processes such as proliferation, migration, apoptosis, differentiation, stress responses, and metabolism. Despite lacking an extensive cytoplasmic signaling domain, CD47 binds to several cytoplasmic proteins, particularly upon engaging with its secreted matricellular ligand, thrombospondin 1. Indeed, the regulatory functions of CD47 are greatly influenced by its interacting partners. These interactions are often cell- and context-specific, adding a further level of complexity. This review addresses the downstream cell-intrinsic signaling pathways regulated by CD47 in various cell types and environments. Some of the key pathways modulated by this receptor include the PI3K/AKT, MAPK/ERK, and nitric oxide signaling pathways, as well as those implicated in glucose, lipid, and mitochondrial metabolism. These pathways play vital roles in maintaining tissue homeostasis, highlighting the importance of understanding the phagocytosis-independent functions of CD47. Given that CD47 expression is dysregulated in a variety of cancers, improving our understanding of the cell-intrinsic signals regulated by this molecule will help advance the development of CD47-targeted therapies.

CD47 是一种普遍表达的细胞表面受体，众所周知，它通过与巨噬细胞表面的信号调节蛋白 α (SIRPα) 相互作用来阻止巨噬细胞介导的吞噬作用。除了在吞噬作用中的作用之外，新兴研究还报道了 CD47 的许多非典型功能，包括调节各种细胞过程，如增殖、迁移、凋亡、分化、应激反应和代谢。尽管缺乏广泛的细胞质信号传导结构域，CD47 仍能与多种细胞质蛋白结合，特别是在与其分泌的基质细胞配体血小板反应蛋白 1 结合后。事实上，CD47 的调节功能很大程度上受到其相互作用伙伴的影响。这些相互作用通常是特定于细胞和环境的，进一步增加了复杂性。本综述讨论了各种细胞类型和环境中 CD47 调节的下游细胞内在信号通路。该受体调节的一些关键途径包括 PI3K/AKT、MAPK/ERK 和一氧化氮信号传导途径，以及与葡萄糖、脂质和线粒体代谢有关的途径。这些途径在维持组织稳态中发挥着至关重要的作用，凸显了了解 CD47 的吞噬独立功能的重要性。鉴于 CD47 表达在多种癌症中失调，提高我们对该分子调节的细胞内在信号的理解将有助于推进 CD47 靶向疗法的开发。