Departments of Cancer Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Front Biosci (Landmark Ed). 2012 Jan 1;17(4):1281-93. doi: 10.2741/3986.
Members of the TGF-beta superfamily exhibit various biological activities, and perturbations of their signaling are linked to certain clinical disorders including cancer. The role of TGF-beta signaling as a tumor suppressor pathway is best illustrated by the presence of inactivating mutations in genes encoding TGF-beta receptors and Smads in human carcinomas. This perspective is further supported by studies of tumor development in mouse models after modulation of receptors and Smads. TGF-beta also controls processes such as cell invasion, immune regulation, and microenvironment alterations that cancer cells may exploit to their advantage for their progression. Consequently, the output of a TGF-beta response is highly situation dependent, across different tissues, and also in cancer in general. Understanding the mechanisms of TGF-beta superfamily signaling is thus important for the development of new ways to treat various types of cancer. This review focuses on recent advances in understanding the Smad dependent TGF-beta pathway as it relates to human carcinogenesis.
TGF-β 超家族成员表现出各种生物学活性，其信号转导的干扰与某些临床疾病有关，包括癌症。TGF-β 信号作为肿瘤抑制途径的作用，最好通过在人类癌中存在编码 TGF-β 受体和 Smads 的基因的失活突变来说明。受体和 Smads 调节后的小鼠模型中的肿瘤发生研究进一步支持了这一观点。TGF-β 还控制细胞侵袭、免疫调节和微环境改变等过程，癌细胞可能会利用这些过程来促进其进展。因此，TGF-β 反应的输出在不同组织中以及在一般癌症中高度依赖于情况。因此，了解 TGF-β 超家族信号转导的机制对于开发治疗各种类型癌症的新方法非常重要。这篇综述重点介绍了理解与人类癌发生相关的 Smad 依赖性 TGF-β 途径的最新进展。
