III 型 TGF-β 受体在人类癌症中的作用。
Roles for the type III TGF-beta receptor in human cancer.
机构信息
Department of Medicine, Duke University Medical Center, Durham, NC, USA.
出版信息
Cell Signal. 2010 Aug;22(8):1163-74. doi: 10.1016/j.cellsig.2010.01.016. Epub 2010 Feb 12.
Transforming growth factor beta (TGF-beta) superfamily ligands have important roles in regulating cellular homeostasis, embryonic development, differentiation, proliferation, immune surveillance, angiogenesis, motility, and apoptosis in a cell type and context specific manner. TGF-beta superfamily signaling pathways also have diverse roles in human cancer, functioning to either suppress or promote cancer progression. The TGF-beta superfamily co-receptor, the type III TGF-beta receptor (TbetaRIII, also known as betaglycan) mediates TGF-beta superfamily ligand dependent as well as ligand independent signaling to both Smad and non-Smad signaling pathways. Loss of TbetaRIII expression during cancer progression and direct effects of TbetaRIII on regulating cell migration, invasion, proliferation, and angiogenesis support a role for TbetaRIII as a suppressor of cancer progression and/or as a metastasis suppressor. Defining the physiological function and mechanism of TbetaRIII action and alterations in TbetaRIII function during cancer progression should enable more effective targeting of TbetaRIII and TbetaRIII mediated functions for the diagnosis and treatment of human cancer.
转化生长因子-β（TGF-β）超家族配体在调节细胞内稳态、胚胎发育、分化、增殖、免疫监视、血管生成、运动和细胞凋亡方面具有重要作用，其作用方式具有细胞类型和背景的特异性。TGF-β 超家族信号通路在人类癌症中也具有多种作用，既能抑制肿瘤的进展，也能促进肿瘤的进展。TGF-β 超家族的共受体，即 III 型 TGF-β 受体（TβRIII，也称为 betaglycan），介导 TGF-β 超家族配体依赖性和配体非依赖性信号转导，作用于 Smad 和非 Smad 信号通路。在癌症进展过程中 TβRIII 表达的缺失以及 TβRIII 对调节细胞迁移、侵袭、增殖和血管生成的直接作用，支持 TβRIII 作为癌症进展的抑制剂和/或转移抑制剂的作用。明确 TβRIII 作用的生理功能和机制，以及 TβRIII 功能在癌症进展过程中的改变，应能更有效地针对 TβRIII 及其介导的功能进行靶向治疗，从而诊断和治疗人类癌症。
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