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TGF - β Signaling Pathway01:16

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Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
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相关实验视频

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Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
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通过致命的EMT抑制TGF-β瘤

Charles J David1, Yun-Han Huang1, Mo Chen2

  • 1Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

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|February 23, 2016
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概括

转化生长因子-β (TGF-β) 信号在癌症中具有双重作用. 在胰腺癌中,TGF-β通过破坏关键的转录网络来诱导致命的上皮层- 介质细胞转换 (EMT),从而促进细胞亡.

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科学领域:

  • 分子生物学
  • 癌症研究
  • 细胞信号传输

背景情况:

  • 转化生长因子-β (TGF-β) 信号在瘤发生过程中表现出双重作用,作为前瘤或瘤抑制剂.
  • 胰腺管腺癌 (PDA) 和其他胃肠道癌症经常表现出Smad4的失活,Smad4是TGF-β信号的关键媒介.
  • 表皮- 介质细胞过渡 (EMT) 通常与促进癌症进展有关.

研究的目的:

  • 研究TGF-β信号传递在胰腺管腺癌 (PDA) 中的双重作用.
  • 阐明TGF-β信号影响PDA中的瘤发生和细胞命运的机制.
  • 了解Smad4,EMT和PDA中的转录因子之间的相互作用.

主要方法:

  • 研究了PDA细胞中的TGF-β信号通路.
  • 分析了TGF-β诱导的上皮介质过渡 (EMT).
  • 研究了Smad4,Sox4和Klf5在PDA细胞行为中的作用.
  • 研究EMT对转录因子的影响.

主要成果:

  • 在PDA细胞中TGF-β诱导EMT,矛盾的是,通过将Sox4从瘤形成强化剂转化为瘤形成促进剂来促进亡.
  • 通过抑制胃肠道主调节器Klf5,EMT破坏了转录系统,该调节器通常与Sox4合作进行瘤生成.
  • Smad4对于EMT至关重要,但对于TGF-β诱导的Sox4上调至关重要,这表明这些途径的分离.

结论:

  • 在PDA中,TGF-β通过EMT介导的关键谱系特异性转录网络的破坏来发挥瘤抑制功能.
  • 在PDA中,EMT与Sox4和Klf5等转录因子之间的相互作用决定了细胞命运.
  • 了解这些复杂的信号相互作用对于开发胰腺癌向疗法至关重要.