Collagen I promotes epithelial-to-mesenchymal transition in lung cancer cells via transforming growth factor-β signaling
Collagen I promotes epithelial-to-mesenchymal transition in lung cancer cells via transforming growth factor-β signaling
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DOI：
10.1165/rcmb.2007-0071oc
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发表时间：
2008-01-01
影响因子：
6.4
通讯作者：
Wheelock, Margaret J.
中科院分区：
文献类型：
--
作者：
Shintani, Yasushi;Maeda, Masato;Wheelock, Margaret J.
上皮向间充质转化(EMT)是上皮细胞失去其极性并向间充质表型转化的基本生物学过程。当癌细胞侵入邻近组织时，它们使用一种类似于EMT的机制，了解推动这种转变的分子机制将有助于研究防止转移的新靶点。细胞外刺激，如生长因子，和它们的胞内效应物共同促进EMT。在像肺癌这样的高度纤维化的癌症中，人们认为细胞外基质分子，包括胶原，可以启动促进EMT的信号。在这里，我们提供的数据表明，I型胶原诱导非小细胞肺癌细胞系的EMT，这是通过阻断转化生长因子(TGF)-β3信号来阻止的。此外，我们还发现，肌醇磷脂3-激酶和细胞外信号相关激酶信号转导的抑制剂可以阻止I型胶原诱导的EMT，后者可以促进这些细胞中转化生长因子-β3mRNA的转录。因此，我们的数据与I型胶原通过激活自分泌的转化生长因子-β3信号在肺癌细胞中诱导EMT的假设是一致的。表皮生长因子似乎也通过一种依赖于转化生长因子的机制启动EMT。
Epithelial-to-mesenchymal transition (EMT) is a fundamental biological process whereby epithelial cells lose their polarity and undergo a transition to a mesenchymal phenotype. When cancer cells invade adjacent tissues, they use a mechanism akin to EMT, and understanding the molecular mechanisms that drive this transition will facilitate studies into new targets for prevention of metastasis. Extracellular stimuli, such as growth factors, and their cytosolic effectors cooperate to promote EMT. In highly fibrotic cancers like lung cancer, it is thought that extracellular matrix molecules, including collagen, can initiate signals that promote EMT. Here, we present data showing that collagen I induces EMT in non-small cell lung cancer cell lines, which is prevented by blocking transforming growth factor (TGF)-beta 3 signaling. In addition, we show that collagen I-incluced EMT is prevented by inhibitors of phosphoinositide 3-kinase and extracellular signal-related kinase signaling, which promotes transcription of TGF-beta 3 mRNA in these cells. Thus, our data are consistent with the hypothesis that collagen I induces EMT in lung cancer cells by activating autocrine TGF-beta 3 signaling. Epidermal growth factor also seems to initiate EMT via a TGF-dependent mechanism.