Department of Biochemistry and Molecular Biology, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, University Hospital Cancer Center, 205 South Orange Avenue, Newark, NJ 07103, USA.
Carcinogenesis. 2010 Oct;31(10):1710-7. doi: 10.1093/carcin/bgq155. Epub 2010 Jul 23.
Resistance to transforming growth factor (TGF) β-mediated tumor suppression in melanoma appears to be a crucial step in tumor aggressiveness since it is usually coupled with the ability of TGFβ to drive the oncogenic process via autocrine and paracrine effects. In this review, we will focus mainly on the mechanisms of escape from TGFβ-induced cell cycle arrest because the mechanisms of resistance to TGFβ-mediated apoptosis are still essentially speculative. As expected, some of these mechanisms can directly affect the function of the main downstream effectors of TGFβ, Smad2 and Smad3, resulting in compromised Smad-mediated antiproliferative activity. Other mechanisms can counteract or overcome TGFβ-mediated cell cycle arrest independently of the Smads. In melanoma, some models of resistance to TGFβ have been suggested and will be described. In addition, we propose additional models of resistance taking into consideration the information available on the dysregulation of fundamental cellular effectors and signaling pathways in melanoma.
在黑色素瘤中，对转化生长因子 (TGF) β介导的肿瘤抑制的抗性似乎是肿瘤侵袭性的关键步骤，因为它通常与 TGFβ 通过自分泌和旁分泌作用驱动致癌过程的能力相关。在这篇综述中，我们将主要关注逃避 TGFβ 诱导的细胞周期阻滞的机制，因为对 TGFβ 介导的细胞凋亡的抗性机制仍然在很大程度上是推测性的。正如预期的那样，其中一些机制可以直接影响 TGFβ 的主要下游效应子 Smad2 和 Smad3 的功能，从而削弱 Smad 介导的抗增殖活性。其他机制可以独立于 Smads 来对抗或克服 TGFβ 介导的细胞周期阻滞。在黑色素瘤中，已经提出了一些 TGFβ 抗性的模型，并将对其进行描述。此外，我们提出了其他的抗性模型，同时考虑了黑色素瘤中基本细胞效应器和信号通路失调的相关信息。
