MITF reprograms the extracellular matrix and focal adhesion in melanoma.
MITF reprograms the extracellular matrix and focal adhesion in melanoma.
复制标题
MITF在黑色素瘤中重新编程细胞外基质和局灶性粘附。
DOI：
10.7554/elife.63093
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发表时间：
2021-01-13
期刊：
影响因子：
7.7
通讯作者：
Steingrimsson E
中科院分区：
文献类型：
--
作者：
Dilshat R;Fock V;Kenny C;Gerritsen I;Lasseur RMJ;Travnickova J;Eichhoff OM;Cerny P;Möller K;Sigurbjörnsdóttir S;Kirty K;Einarsdottir BÓ;Cheng PF;Levesque M;Cornell RA;Patton EE;Larue L;de Tayrac M;Magnúsdóttir E;Ögmundsdóttir MH;Steingrimsson E
小眼球相关转录因子(MITF)是黑素细胞发育和分化的重要调节因子。它在黑色素瘤中也扮演着重要的角色，在黑色素瘤中，它被描述为一个分子变阻器，根据活动水平，允许在不同的细胞状态之间进行可逆切换。在这里，我们表明，MITF直接抑制与细胞外基质(ECM)和局部黏附通路相关的基因在人黑色素瘤细胞中的表达，以及上皮到间充质转化(EMT)的调节因子，如CDH2，从而影响细胞形态和细胞-基质相互作用。重要的是，我们证明了MITF的这些效应是可逆的，正如变阻器模型所预期的那样。在MITF基因敲除后，焦点粘附点的数量增加，这是在耐药黑色素瘤中观察到的特征。缺乏MITF的细胞类似于在人类和斑马鱼黑色素瘤中观察到的微小残留病细胞。我们的结果表明，MITF作为基因表达的抑制因子发挥了关键作用，并以细胞自主的方式积极参与了黑色素瘤细胞微环境的塑造。
The microphthalmia-associated transcription factor (MITF) is a critical regulator of melanocyte development and differentiation. It also plays an important role in melanoma where it has been described as a molecular rheostat that, depending on activity levels, allows reversible switching between different cellular states. Here, we show that MITF directly represses the expression of genes associated with the extracellular matrix (ECM) and focal adhesion pathways in human melanoma cells as well as of regulators of epithelial-to-mesenchymal transition (EMT) such as CDH2, thus affecting cell morphology and cell-matrix interactions. Importantly, we show that these effects of MITF are reversible, as expected from the rheostat model. The number of focal adhesion points increased upon MITF knockdown, a feature observed in drug-resistant melanomas. Cells lacking MITF are similar to the cells of minimal residual disease observed in both human and zebrafish melanomas. Our results suggest that MITF plays a critical role as a repressor of gene expression and is actively involved in shaping the microenvironment of melanoma cells in a cell-autonomous manner.
影响因子：
8
作者：
Stylianou N;Lehman ML;Wang C;Fard AT;Rockstroh A;Fazli L;Jovanovic L;Ward M;Sadowski MC;Kashyap AS;Buttyan R;Gleave ME;Westbrook TF;Williams ED;Gunter JH;Nelson CC;Hollier BG
通讯作者：
Hollier BG