Caja Laia, Bellomo Claudia, Moustakas Aristidis
Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Box 582, SE-751 23 Uppsala, Sweden; Ludwig Cancer Research, Science for Life Laboratory, Uppsala University, Box 595, SE-751 24 Uppsala, Sweden.
Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Box 582, SE-751 23 Uppsala, Sweden; Ludwig Cancer Research, Science for Life Laboratory, Uppsala University, Box 595, SE-751 24 Uppsala, Sweden.
FEBS Lett. 2015 Jun 22;589(14):1588-97. doi: 10.1016/j.febslet.2015.04.058. Epub 2015 May 6.
Members of the transforming growth factor β (TGF-β) family are implicated in the biology of several cancers. Here we focus on malignancies of the brain and examine the TGFβ and the bone morphogenetic protein (BMP) signaling branches of the family. These pathways exhibit context-dependent actions during tumorigenesis, acting either as tumor suppressors or as pro-tumorigenic agents. In the brain, the TGF-βs associate with oncogenic development and progression to the more malignant state. Inversely, the BMPs suppress tumorigenic potential by acting as agents that induce tumor cell differentiation. The latter has been best demonstrated in grade IV astrocytomas, otherwise known as glioblastoma multiforme. We discuss how the actions of TGF-βs and BMPs on cancer stem cells may explain their effects on tumor progression, and try to highlight intricate mechanisms that may link tumor cell differentiation to invasion. The focus on TGF-β and BMP and their actions in brain malignancies provides a rich territory for mechanistic understanding of tumor heterogeneity and suggests ways for improved therapeutic intervention, currently being addressed by clinical trials.
转化生长因子β（TGF-β）家族成员与多种癌症的生物学特性有关。在此，我们聚焦于脑恶性肿瘤，并研究该家族的TGFβ和骨形态发生蛋白（BMP）信号分支。这些信号通路在肿瘤发生过程中表现出依赖于背景的作用，既可以作为肿瘤抑制因子，也可以作为促肿瘤发生因子。在大脑中，TGF-β与致癌发展以及向更恶性状态的进展相关。相反，BMP通过作为诱导肿瘤细胞分化的因子来抑制肿瘤发生潜能。这一点在IV级星形细胞瘤（即多形性胶质母细胞瘤）中得到了最好的证明。我们讨论了TGF-β和BMP对癌症干细胞的作用如何解释它们对肿瘤进展的影响，并试图突出可能将肿瘤细胞分化与侵袭联系起来的复杂机制。对TGF-β和BMP及其在脑恶性肿瘤中的作用的关注为深入理解肿瘤异质性提供了丰富的领域，并为改进治疗干预提供了思路，目前临床试验正在探讨这些问题。
