PAX3 and SOX10 activate MET receptor expression in melanoma.
PAX3 and SOX10 activate MET receptor expression in melanoma.
复制标题
PAX3 和 SOX10 激活黑色素瘤中的 MET 受体表达。
DOI：
10.1111/j.1755-148x.2010.00667.x
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发表时间：
2010-04
影响因子：
4.3
通讯作者：
Lang D
中科院分区：
文献类型：
--
作者：
Mascarenhas JB;Littlejohn EL;Wolsky RJ;Young KP;Nelson M;Salgia R;Lang D
黑色素瘤是一种分子病理学知之甚少的癌症。我们发现转录因子PAX 3，SOX 10，MITF和酪氨酸激酶受体MET在黑色素瘤细胞系和原发性肿瘤中表达。原发性肿瘤标本中MET表达的分析显示，27/40（68%）的样本显示MET表达增加，并且该表达与PAX 3、SOX 10和MITF的平行表达高度相关。PAX 3和MITF独立地结合MET启动子中的元件，没有协同激活或抑制的证据。SOX 10不直接单独激活MET基因，但可以与PAX 3或MITF协同激活MET表达。在黑色素瘤细胞中，有证据表明PAX 3介导的MET诱导有两种途径：1）基因的直接激活，和2）通过MITF的间接调节。SK-MEL 23黑色素瘤细胞具有完整的这两种途径，而SK-MEL 28黑色素瘤细胞仅具有第一种途径。综上所述，我们发现PAX 3、SOX 10和MITF通过调节MET基因在黑色素瘤细胞中发挥积极作用。因此，MET通过促进迁移、侵袭、抗凋亡和肿瘤细胞生长来促进黑色素瘤癌症表型。
Melanoma is a cancer with a poorly understood molecular pathobiology. We find the transcription factors PAX3, SOX10, MITF, and the tyrosine kinase receptor MET expressed in melanoma cell lines and primary tumors. Analysis for MET expression in primary tumor specimens showed 27/40 (68%) of the samples displayed an increased expression of MET, and this expression was highly correlated with parallel expression of PAX3, SOX10, and MITF. PAX3 and MITF bind to elements in the MET promoter independently, without evidence of either synergistic activation or inhibition. SOX10 does not directly activate the MET gene alone, but can synergistically activate MET expression with either PAX3 or MITF. In melanoma cells, there was evidence of two pathways for PAX3 mediated MET induction: 1) direct activation of the gene, and 2) indirect regulation through MITF. SK-MEL23 melanoma cells have both of these pathways intact, while SK-MEL28 melanoma cells only have the first pathway. In summary, we find that PAX3, SOX10 and MITF play an active role in melanoma cells by regulating the MET gene. In consequence, MET promotes the melanoma cancer phenotype by promoting migration, invasion, resistance to apoptosis, and tumor cell growth.