Menin represses malignant phenotypes of melanoma through regulating multiple pathways.
Menin represses malignant phenotypes of melanoma through regulating multiple pathways.
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Menin 通过调节多种途径抑制黑色素瘤的恶性表型
DOI：
10.1111/j.1582-4934.2010.01222.x
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发表时间：
2011-11
影响因子：
5.3
通讯作者：
Jin GH
中科院分区：
文献类型：
--
作者：
Gao SB;Feng ZJ;Xu B;Chen Y;Zheng HH;Yin P;Hua X;Jin GH
大量遗传学证据表明，染色体11 q参与调节恶性黑色素瘤的发生和发展。位于染色体11 q13的MEN 1基因突变使个体易患多发性内分泌瘤1型（MEN 1）家族综合征。MEN 1患者发生原发性恶性黑色素瘤，提示MEN 1综合征与黑色素瘤发生之间存在潜在联系，但确切的分子机制尚不清楚。在这里，我们表明MEN 1基因通过多种信号通路抑制黑色素瘤细胞的恶性表型。MEN 1基因的产物menin的异位表达在体外和体内均能显著抑制黑色素瘤细胞的增殖和迁移。其抑制作用部分通过抑制生长因子多效生长因子（PTN）和受体蛋白酪氨酸磷酸酶（RPTP）β/β的表达，同时降低磷脂酰肌醇3-激酶（pI 3 K）的表达，降低粘着斑激酶（FAK）和细胞外信号调节激酶（ERK 1/2）的磷酸化水平来实现。有趣的是，menin的表达减少与黑素瘤细胞中MEN 1启动子CpG岛的高甲基化有关。两者合计，这些发现表明，以前未被赞赏的功能menin在抑制恶性表型的黑色素瘤和解开一个新的机制，涉及调节PTN信号的menin在黑色素瘤的发展和进展。
Substantial genetic evidence suggests that chromosome 11q is involved in regulating initiation and progression of malignant melanomas. Mutations of the MEN1 gene, located in chromosome 11q13, predispose individuals to the multiple endocrine neoplasia type 1 (MEN1) familial syndrome. MEN1 patients develop primary malignant melanoma, suggesting a potential link between MEN1 syndrome and development of melanomas, but the precise molecular mechanism is poorly understood. Here we show that the MEN1 gene suppresses malignant phenotypes of melanoma cells through multiple signalling pathways. Ectopic expression of menin, the product of MEN1 gene, significantly inhibited melanoma cell proliferation and migration in vitro and in vivo. The inhibition was partly achieved through suppressing expression of growth factor pleiotrophin (PTN) and receptor protein tyrosine phosphatase (RPTP) β/ζ, accompanied with the reduced expression of phosphatidylinositol 3‐kinase (pI3K) and decreased phosphorylation of focal adhesion kinase (FAK) and extracellular signal regulated kinase (ERK1/2). Interestingly, reduced expression of menin was associated with hypermethylation of the CpG islands of the MEN1 promoter in melanoma cells. Taken together, these findings suggest a previously unappreciated function for menin in suppressing malignant phenotypes of melanomas and unravel a novel mechanism involving in regulating PTN signalling by menin in development and progression of melanomas.
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影响因子：
64.5
作者：
Heidorn SJ;Milagre C;Whittaker S;Nourry A;Niculescu-Duvas I;Dhomen N;Hussain J;Reis-Filho JS;Springer CJ;Pritchard C;Marais R
通讯作者：
Marais R
影响因子：
16
作者：
Hughes, CM;Rozenblatt-Rosen, O;Meyerson, M
通讯作者：
Meyerson, M
影响因子：
4.8
作者：
Lu, KV;Jong, KA;Mischel, PS
通讯作者：
Mischel, PS
影响因子：
4.8
作者：
Mikelis, Constantinos;Sfaelou, Evanthia;Papadimitriou, Evangelia
通讯作者：
Papadimitriou, Evangelia
DOI：
10.1073/pnas.93.25.14753
发表时间：
1996-12-10
影响因子：
11.1
作者：
Czubayko, F;Schulte, AM;Wellstein, A
通讯作者：
Wellstein, A