TGF-beta Signaling in Cancer Treatment
TGF-beta Signaling in Cancer Treatment
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DOI：
10.2174/13816128113199990591
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发表时间：
2014-05-01
影响因子：
3.1
通讯作者：
Sancho, Patricia
中科院分区：
文献类型：
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作者：
Fabregat, Isabel;Fernando, Joan;Sancho, Patricia
转化生长因子-β（TGF-β）属于细胞因子超家族，其作用于质膜上的蛋白激酶受体以诱导过多的生物信号，所述生物信号调节细胞生长和死亡、分化、免疫应答、血管生成和炎症。其途径的失调导致多种病理，包括癌症。TGF-！是上皮细胞中重要的调节性肿瘤抑制因子，其早期抑制增殖并诱导凋亡。然而，肿瘤细胞发展机制，以克服TGF-！- 诱导的抑制效应。一旦发生这种情况，细胞可能会对这种细胞因子产生反应，诱导其他有助于肿瘤进展的效应。的确，TGF-！诱导上皮-间充质转化（EMT），这是一个在肿瘤细胞中有利并促进迁移和侵袭的过程。此外，TGF-！介导促有丝分裂生长因子的产生，其刺激肿瘤增殖和存活。最后，TGF-！是一种众所周知的免疫抑制因子和促血管生成因子。许多研究已经确定了TGF-！1，其与肿瘤进展、转移、血管生成和不良预后结果相关。出于这些原因，不同的策略来阻止TGF-！已经开发了癌症通路中的各种药物，它们可以分为：（1）阻断抗体和配体陷阱;（2）反义寡核苷酸;（3）T！RII和/或ALK 5抑制剂;（4）基于免疫应答的策略;（5）TGF-β 1的其他抑制剂;通路在这篇综述中，我们将概述TGF-！信号在肿瘤发生的调节，我们将剖析如何靶向TGF-！可能有助于对抗癌症。
The transforming growth factor-beta (TGF-!) belongs to a superfamily of cytokines that act on protein kinase receptors at the plasma membrane to induce a plethora of biological signals that regulate cell growth and death, differentiation, immune response, angiogenesis and inflammation. Dysregulation of its pathway contributes to a broad variety of pathologies, including cancer. TGF-! is an important regulatory tumor suppressor factor in epithelial cells, where it early inhibits proliferation and induces apoptosis. However, tumor cells develop mechanisms to overcome the TGF-! -induced suppressor effects. Once this occurs, cells may respond to this cytokine inducing other effects that contribute to tumor progression. Indeed, TGF-! induces epithelial-mesenchymal transition (EMT), a process that is favored in tumor cells and facilitates migration and invasion. Furthermore, TGF-! mediates production of mitogenic growth factors, which stimulate tumor proliferation and survival. Finally, TGF-! is a well known immunosuppressor and pro-angiogenic factor. Many studies have identified the overexpression of TGF-! 1 in various types of human cancer, which correlates with tumor progression, metastasis, angiogenesis and poor prognostic outcome. For these reasons, different strategies to block TGF-! pathway in cancer have been developed and they can be classified in: (1) blocking antibodies and ligand traps; (2) antisense oligos; (3) T! RII and/or ALK5 inhibitors; (4) immune response-based strategies; (5) other inhibitors of the TGF-! pathway. In this review we will overview the two faces of TGF-! signaling in the regulation of tumorigenesis and we will dissect how targeting the TGF-! pathway may contribute to fight against cancer.