Kitisin Krit, Saha Tapas, Blake Tiffany, Golestaneh Nady, Deng Merlyn, Kim Christine, Tang Yi, Shetty Kirti, Mishra Bibhuti, Mishra Lopa
Laboratory of Cancer Genetics and Digestive Diseases, Department of Surgery, and Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20007, USA.
Sci STKE. 2007 Aug 14;2007(399):cm1. doi: 10.1126/stke.3992007cm1.
The transforming growth factor-beta (TGF-beta) superfamily comprises nearly 30 growth and differentiation factors that include TGF-betas, activins, inhibins, and bone morphogenetic proteins (BMPs). Multiple members of the TGF-beta superfamily serve key roles in stem cell fate commitment. The various members of the family can exhibit disparate roles in regulating the biology of embryonic stem (ES) cells and tumor suppression. For example, TGF-beta inhibits proliferation of multipotent hematopoietic progenitors, promotes lineage commitment of neural precursors, and suppresses epithelial tumors. BMPs block neural differentiation of mouse and human ES cells, contribute to self-renewal of mouse ES cells, and also suppress tumorigenesis. ES cells and tumors may be exposed to multiple TGF-beta members, and it is likely that the combination of growth factors and cross-talk among the intracellular signaling pathways is what precisely defines stem cell fate commitment. This Connections Map Pathway in the Database of Cell Signaling integrates signaling not only from TGF-beta and BMP but also from the ligands nodal and activin, and describes the role of the signaling pathways activated by these ligands in mammalian development. Much of the evidence for the connections shown comes from studies on mouse and human ES cells or mouse knockouts. This pathway is important for understanding not only stem cell biology, but also the molecular effectors of TGF-beta and BMP signaling that may contribute to cancer suppression or progression and thus are potential targets for therapeutic intervention.
转化生长因子-β（TGF-β）超家族包含近30种生长和分化因子，其中包括TGF-β、激活素、抑制素和骨形态发生蛋白（BMP）。TGF-β超家族的多个成员在干细胞命运决定中发挥关键作用。该家族的不同成员在调节胚胎干细胞（ES细胞）生物学特性和肿瘤抑制方面可能表现出不同的作用。例如，TGF-β抑制多能造血祖细胞的增殖，促进神经前体细胞的谱系分化，并抑制上皮肿瘤。BMP阻止小鼠和人类ES细胞的神经分化，有助于小鼠ES细胞的自我更新，同时也抑制肿瘤发生。ES细胞和肿瘤可能会接触到多种TGF-β成员，很可能是生长因子的组合以及细胞内信号通路之间的相互作用精确地决定了干细胞的命运。细胞信号数据库中的这条连接图谱通路不仅整合了来自TGF-β和BMP的信号，还整合了来自配体节点蛋白和激活素的信号，并描述了这些配体激活的信号通路在哺乳动物发育中的作用。所示连接的许多证据来自对小鼠和人类ES细胞或小鼠基因敲除的研究。这条通路不仅对于理解干细胞生物学很重要，而且对于理解TGF-β和BMP信号的分子效应器也很重要，这些效应器可能有助于癌症抑制或进展，因此是治疗干预的潜在靶点。
