Urban P, Rabajdová M, Veliká B, Špaková I, Bolerázska B, Mareková M
Klin Onkol. 2016 Fall;29(5):347-350. doi: 10.14735/amko2016347.
Malignant melanoma is one of the most aggressive types of cancers. Melanoma is derived from pigment-producing cells, melanocytes, which are characterized by a specific survival mechanism. Microphthalmia-associated transcription factor (MITF-M) plays a role in the metabolism of melanoma and is involved in the regulation of the expression of multiple genes mediating processes such as melanogenesis, proliferation, differentiation, and melanocyte survival. The expression of this transcription factor in melanocytes is activated by several signaling pathways, and reduced expression or function of MITF-M can cause the dysregulation of anti-apoptotic mechanisms. MITF-M is also involved in matrix metalloproteinase 14 (MMP14) activity, which is responsible for shape changes in melanocytes and increases in their motility and invasiveness. Very low levels of expression of MITF-M are found in human melanocytes with an invasive phenotype, indicating that this transcription factor acts as a suppressor of the metastatic process. Cancer cells with low expression of cytosolic/nuclear β-catenin have a small amount of MITF-M 14 that is insufficient to inhibit MMP transcription. The enzyme catalyzes the degradation of laminin and fibronectin, thereby changing the shape of melanocytes, which leads to their increased mobility and invasiveness.
This review describes the regulatory pathway of MITF-M activation, its involvement in the proliferation of transformed melanocytes, and its role in increasing the invasiveness of malignant melanoma. A detailed understanding of the MITF-M signaling pathway is highly topical and could help to develop new diagnostic and therapeutic applications for patients with malignant melanoma.Key words: neoplastic cell transformation - melanoma - MITF transcription factorThis work was supported by grant projects VEGA 1/0115/14 and VEGA 1/0873/16.The authors declare they have no potential confl icts of interest concerning drugs, products, or services used in the study.The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 4. 12. 2015Accepted: 14. 6. 2016.
恶性黑色素瘤是最具侵袭性的癌症类型之一。黑色素瘤起源于产生色素的细胞，即黑素细胞，其具有特定的生存机制。小眼相关转录因子（MITF - M）在黑色素瘤的代谢中发挥作用，并参与调节多个基因的表达，这些基因介导诸如黑素生成、增殖、分化和黑素细胞存活等过程。该转录因子在黑素细胞中的表达由多种信号通路激活，MITF - M表达或功能的降低可导致抗凋亡机制失调。MITF - M还参与基质金属蛋白酶14（MMP14）的活性，MMP14负责黑素细胞的形态变化，并增加其运动性和侵袭性。在具有侵袭性表型的人类黑素细胞中发现MITF - M的表达水平非常低，这表明该转录因子作为转移过程的抑制因子发挥作用。胞质/核β - 连环蛋白低表达的癌细胞中，MITF - M 14的含量不足以抑制MMP转录。该酶催化层粘连蛋白和纤连蛋白的降解，从而改变黑素细胞的形状，导致其运动性和侵袭性增加。
本综述描述了MITF - M激活的调控途径、其在转化黑素细胞增殖中的作用以及其在增加恶性黑色素瘤侵袭性中的作用。对MITF - M信号通路的详细了解具有高度的时效性，有助于为恶性黑色素瘤患者开发新的诊断和治疗应用。关键词：肿瘤细胞转化 - 黑色素瘤 - MITF转录因子
本研究得到了VEGA 1/0115/14和VEGA 1/0873/16资助项目的支持。
作者声明他们在研究中使用的药物、产品或服务方面没有潜在的利益冲突。
编辑委员会声明该手稿符合ICMJE对生物医学论文的推荐要求。
2015年12月4日
2016年6月14日
