Biotechnology Group, Biological Sciences and Technology Division, CSIR-North East Institute of Science and Technology, Jorhat, Assam 785006, India; Academy of Scientific and Innovative Research (AcSIR), CSIR, North East Institute of Science and Technology, Jorhat, Assam 785006, India.
Department of Biotechnology, Indian Institute of Technology Roorkee (IITR), Roorkee, Uttarakhand 247667, India.
Exp Cell Res. 2018 Jul 15;368(2):137-146. doi: 10.1016/j.yexcr.2018.04.014. Epub 2018 Apr 16.
The major hallmarks of Epithelial-Mesenchymal Transition (EMT) is the loss of epithelial cell polarity and loss of expression of the cell- cell adhesion molecule like E-cadherin and acquired mesenchymal cells marker called N-Cadherin. This phenotypical changes of E-M plasticity of cells is extensively considered to be a crucial factor for tumor cells invasion and cancer metastasis; landmark events for transforming a locally growing tumor (benign tumor) into a systemic and live-threatening disease (malignant tumor). Cadherin molecules are adherens junction proteins and expressed as multiple isoforms. Cadherin switching occurs during normal tissue developmental processes; also recapitulates the increasing aggressive behavior and metastatic nature of cancer cells when E-Cadherin converts to N-Cadherin, in particular. There are several mechanisms established that cadherin switching and some of the underlying pathways involves multiple steps associated with migration and invasion of cancer cells, and finally colonization of micro metastatic lesions to form macro-metastasis. Inhibition of metastasis is complicated by the plasticity of cancer cells behaviors and the evolving nature of microenvironment. Although there is no clear evidence how that dynamic structural switching of cadherin family member occurs, stabilized and eventually influence cell behavior, phenotypic transformations and initiate tumorigenesis. Therefore, we emphasize here the major functions of over 20 existing human cadherins in tissue integrity and stability as well as mechanistic understanding on recent work of cadherin ectodomain-mediated adhesion, functional studies of the cell-cell adhesion through key signaling intermediates interacting with other binding partners. We hope understanding on how the dynamic all existing cadherins influence the cell behavior can be targeted to design possible therapeutic interventions to combat its activity and prevent tumor cell growth, invasion and metastasis.
上皮-间质转化 (EMT) 的主要特征是上皮细胞极性的丧失和细胞-细胞黏附分子如 E-钙黏蛋白的表达丧失以及获得间充质细胞标志物 N-钙黏蛋白。细胞的这种 E-M 可塑性的表型变化被广泛认为是肿瘤细胞侵袭和癌症转移的关键因素；是将局部生长的肿瘤（良性肿瘤）转化为全身性和危及生命的疾病（恶性肿瘤）的标志性事件。钙黏蛋白分子是黏着连接蛋白，有多种同工型表达。钙黏蛋白转换发生在正常组织发育过程中；当 E-钙黏蛋白转换为 N-钙黏蛋白时，特别是在癌细胞的侵袭行为和转移性增加时，也会重新出现。已经建立了几种机制，钙黏蛋白转换和一些潜在途径涉及与癌细胞迁移和侵袭相关的多个步骤，最终导致微转移灶的定植并形成大转移灶。转移的抑制因癌细胞行为的可塑性和微环境的不断变化而变得复杂。尽管没有明确的证据表明钙黏蛋白家族成员如何发生动态结构转换，但稳定并最终影响细胞行为、表型转化并引发肿瘤发生。因此，我们在这里强调 20 多种现有人类钙黏蛋白在组织完整性和稳定性中的主要功能，以及钙黏蛋白外显子介导的黏附的最新工作的机制理解，通过与其他结合伴侣相互作用的关键信号转导中间物进行细胞-细胞黏附的功能研究。我们希望了解动态所有现有钙黏蛋白如何影响细胞行为，可以针对其活性进行靶向设计，以进行可能的治疗干预，从而防止肿瘤细胞生长、侵袭和转移。
