Seoane Joan
Institució Catalana de Recerca i Estudis Avançats (ICREA), Medical Oncology Program Vall d'Hebron University Hospital Research Institute, Barcelona, Spain.
Carcinogenesis. 2006 Nov;27(11):2148-56. doi: 10.1093/carcin/bgl068. Epub 2006 May 12.
Transforming growth factor-beta (TGFbeta) has a crucial role in tissue homeostasis and disruption of the TGFbeta pathway has been implicated in many human diseases including cancer. As a potent inhibitor of epithelial cell proliferation, TGFbeta is a tumor suppressor. Tumor cells evade the antitumoral effect of TGFbeta, either by acquiring somatic mutations that blunt TGFbeta signaling or by selectively preventing the cytostatic responses to TGFbeta. During tumor progression, TGFbeta not only loses the anti-proliferative response but can also become an oncogenic factor. Recent work has provided insights into the specific molecular mechanisms involved in the loss of the TGFbeta anti-proliferative response. This review is an overview of the mechanisms that lead to the impairment of the tumor-suppressive function of TGFbeta in cancer. The understanding of how the TGFbeta signal is disrupted in cancer might facilitate the design and development of rational and successful therapeutic strategies.
转化生长因子-β（TGFβ）在组织稳态中起关键作用，TGFβ信号通路的破坏与包括癌症在内的许多人类疾病有关。作为上皮细胞增殖的有效抑制剂，TGFβ是一种肿瘤抑制因子。肿瘤细胞通过获得使TGFβ信号减弱的体细胞突变，或通过选择性地阻止对TGFβ的细胞生长抑制反应，来逃避TGFβ的抗肿瘤作用。在肿瘤进展过程中，TGFβ不仅失去抗增殖反应，还可能成为致癌因子。最近的研究工作为TGFβ抗增殖反应丧失所涉及的具体分子机制提供了见解。本综述概述了导致癌症中TGFβ肿瘤抑制功能受损的机制。了解TGFβ信号在癌症中是如何被破坏的，可能有助于设计和开发合理且成功的治疗策略。
