Role of Kindlin-2 in cancer progression and metastasis.
Role of Kindlin-2 in cancer progression and metastasis.
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DOI：
10.21037/atm.2020.03.64
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发表时间：
2020-03
影响因子：
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通讯作者：
Wei Wang;U. Kansakar;V. Markovic;K. Sossey-Alaoui
中科院分区：
文献类型：
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作者：
Wei Wang;U. Kansakar;V. Markovic;K. Sossey-Alaoui
癌症转移是一个复杂和多步骤的过程，其中癌细胞逃离原发部位的限制，在远处部位建立新的驻留。这个多步骤的过程也被称为侵袭-转移级联反应。控制侵袭-转移级联反应的生物学和分子机制，最终导致癌细胞扩散到远处，仍然知之甚少。Kindlin-2（K2）属于4.1-ezrin-ridixin-moesin（FERM）结构域蛋白家族，与β-整联蛋白亚基的胞质尾区相互作用，激活广泛的生物学功能。这些生物学功能包括细胞迁移、分化、癌症起始、发展和侵袭。在这篇综述中，我们将讨论各种分子信号通路，在肿瘤的侵袭-转移级联过程中的K2调节。这些信号通路包括TGFβ、Wnt/β-连环蛋白、Hedgehog、p53和衰老以及癌症干细胞（CSC）维持。我们还将讨论在转录和翻译后水平上调节K2功能的分子信号通路。最后，我们将考虑特异性靶向K2的分子机制作为癌症治疗的新治疗选择。
Cancer metastasis is a complex and multistep process whereby cancer cells escape the confines of the primary site to establish a new residency at distant sites. This multistep process is also known as the invasion-metastasis cascade. The biological and molecular mechanisms that control the invasion-metastasis cascade, which ultimately leads to the spread of cancer cells into distant sites, remain poorly understood. Kindlin-2 (K2) belongs to the 4.1-ezrin-ridixin-moesin (FERM) domain family of proteins, which interact with the cytoplasmic tails of β-integrin subunits, leading to the activation of extensive biological functions. These biological functions include cell migration, differentiation, cancer initiation, development, and invasion. In this review, we will discuss the various molecular signaling pathways that are regulated by K2 during the invasion-metastasis cascade of cancer tumors. These signaling pathways include TGFβ, Wnt/β-Catenin, Hedgehog, p53 and senescence, and cancer stem cell (CSC) maintenance. We will also discuss the molecular signaling pathways that regulate K2 function both at the transcriptional and the posttranslational levels. Finally, we will consider molecular mechanisms to specifically target K2 as novel therapeutic options for cancer treatment.