Stromal control of oncogenic traits expressed in response to the overexpression of GLI2, a pleiotropic oncogene.
Stromal control of oncogenic traits expressed in response to the overexpression of GLI2, a pleiotropic oncogene.
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基质对致癌性状的控制是对多效性致癌基因 GLI2 过度表达的反应。
DOI：
10.1038/onc.2008.421
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发表时间：
2009
期刊：
影响因子：
8
通讯作者：
Albertson,DG
中科院分区：
文献类型：
--
作者：
Snijders,AM;Huey,B;Connelly,ST;Roy,R;Jordan,RCK;Schmidt,BL;Albertson,DG
Hedgehog信号通常在肿瘤中被激活，但仍不清楚GLI 2（一种由该途径激活的转录因子）如何作为致癌基因发挥作用。我们表明，GLI 2是一个多效性癌基因。过表达诱导基因组不稳定性并阻断分化，可能部分由干细胞基因SOX 2的表达增强介导。GLI 2还诱导包皮和舌的转化生长因子（TGF）B1依赖性转分化，但不诱导牙龈成纤维细胞向肌成纤维细胞的转分化，从而产生允许角质形成细胞侵入的环境，所述角质形成细胞处于具有下调的GLI 2的不同分化阶段。因此，上调的GLI 2表达足以诱导肿瘤细胞的许多获得性特征;然而，基质以组织特异性方式决定某些GLI 2致癌性状是否表达。
Hedgehog signaling is often activated in tumors, yet it remains unclear how GLI2, a transcription factor activated by this pathway, acts as an oncogene. We show that GLI2 is a pleiotropic oncogene. The overexpression induces genomic instability and blocks differentiation, likely mediated in part by enhanced expression of the stem cell gene SOX2. GLI2 also induces transforming growth factor (TGF) B1-dependent transdifferentiation of foreskin and tongue, but not gingival fibroblasts into myofibroblasts, creating an environment permissive for invasion by keratinocytes, which are in various stages of differentiation having downregulated GLI2. Thus, upregulated GLI2 expression is sufficient to induce a number of the acquired characteristics of tumor cells; however, the stroma, in a tissue-specific manner, determines whether certain GLI2 oncogenic traits are expressed.