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KRIT1 作为黑色素瘤侵袭性的一个可能的新靶点。

KRIT1 as a possible new player in melanoma aggressiveness.

机构信息

Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Italy.

Plants for Human Health Institute, NC Research Campus, NC State University, NC, USA.

出版信息

Arch Biochem Biophys. 2020 Sep 30;691:108483. doi: 10.1016/j.abb.2020.108483. Epub 2020 Jul 28.

Abstract

Krev interaction trapped protein 1 (KRIT1) is a scaffold protein known to form functional complexes with distinct proteins, including Malcavernin, PDCD10, Rap1 and others. It appears involved in several cellular signaling pathways and exerts a protective role against inflammation and oxidative stress. KRIT1 has been studied as a regulator of endothelial cell functions and represents a determinant in the pathogenesis of Cerebral Cavernous Malformation (CCM), a cerebrovascular disease characterized by the formation of clusters of abnormally dilated and leaky blood capillaries, which predispose to seizures, neurological deficits and intracerebral hemorrhage. Although KRIT1 is ubiquitously expressed, few studies have described its involvement in pathologies other than CCM including cancer. Cutaneous melanoma represents the most fatal skin cancer due to its high metastatic propensity. Despite the numerous efforts made to define the signaling pathways activated during melanoma progression, the molecular mechanisms at the basis of melanoma growth, phenotype plasticity and resistance to therapies are still under investigation.

摘要

血管相互作用陷窝蛋白 1(KRIT1)是一种支架蛋白,已知其与多种蛋白形成功能性复合物,包括 Malcavernin、PDCD10、Rap1 等。它似乎参与了几种细胞信号通路,并发挥了抗炎和抗氧化应激的保护作用。KRIT1 被研究为内皮细胞功能的调节剂,是脑静脉畸形(CCM)发病机制的决定因素,CCM 是一种脑血管疾病,其特征是形成簇状异常扩张和渗漏的毛细血管,易发生癫痫、神经功能缺损和颅内出血。尽管 KRIT1 广泛表达,但很少有研究描述其除 CCM 以外的病理学参与,包括癌症。皮肤黑色素瘤由于其高转移性倾向,是最致命的皮肤癌。尽管为了确定黑色素瘤进展过程中激活的信号通路做出了许多努力,但黑色素瘤生长、表型可塑性和对治疗的抵抗的分子机制仍在研究中。

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