ZEB1 and oncogenic Ras constitute a regulatory switch for stimulus‐dependent E‐cadherin downregulation

Abstract

E-cadherin, encoded by the CDH1 gene, is a calcium-dependent cell adhesion molecule localized in adherens junctions of epithelial cells. 1 The downregulation of E-cadherin expression is considered one of the hallmarks of cells undergoing epithelial-mesenchymal transition (EMT) and is closely associated with cell invasion. It has been reported that interference of E-cadherin function by neutralizing antibodies results in the acquirement of invasive properties by nontransformed epithelial cells. 2 Moreover, an inverse correlation between invasiveness and E-cadherin expression level was observed in various human carcinoma cell lines, and the invasiveness of E-cadherin-negative cancer cells was prevented by its exogenous expression. 3 E-cadherin is also a putative tumor suppressor as it suppresses the progression from adenoma to carcinoma 4 and is involved in contact inhibition, thereby suppressing excessive cell growth. 5 Furthermore, its downregulation facilitates immune escape 6 and leads to drug resistance in epidermal growth factor receptor-mutated cancer cells. 7 Consistently, loss of E-cadherin expression is often detected in invasive cancer cells and correlates with a poor prognosis in some

MCP mediated active targeting calcium phosphate hybrid nanoparticles for the treatment of orthotopic drug-resistant colon cancer

“…Studies have shown that E-cadherin is a key molecule to maintain the adhesion between cancer cells [36][37][38]. Inhibiting the expression of E-cadherin can reduce the adhesion between cancer cells and lead to the shedding of cancer cells from primary cancer tissue, which induces the metastasis of colon cancer [39,40]. In addition, MMP-9 can degrade E-cadherin, subsequently reduce the adhesion between cancer cells [41,42].…”

Role of miRNAs in Normal Endometrium and in Endometrial Disorders: Comprehensive Review

“…The let-7 family has been found to be involved in the promotion of EMT in endometrial carcinosarcomas [85]. The action of miR-141 and miR-200 is thought to be based on the regulation of ZEB1/ZEB2 expression involved in the regulation of E-cadherin expression [86][87][88]. Let-7 is thought to regulate the expression of the high mobility group AT-hook 2 (HMGA2), an embryonic nuclear factor [85], which in turn regulates the expression of Snail, Slug, ZEB1, and ZEB2 inducing EMT [89].…”

“…Let-7 is thought to regulate the expression of the high mobility group AT-hook 2 (HMGA2), an embryonic nuclear factor [85], which in turn regulates the expression of Snail, Slug, ZEB1, and ZEB2 inducing EMT [89]. miR-34b Down-regulated [90] miR-101 Down-regulated [90] miR-106 Promotion of EMT [91] Up-regulated [91] miR-133 Up-regulated by progesterone [31] Promotion of EMT [84]; promotion of endometrial epithelial cell proliferation [31] Down-regulated [90] miR-141 Promotion of EMT [84]; regulation of ZEB1/ZEB2 expression [86][87][88] Up-regulated [84,90] miR-144 Promotion of EMT [91] Up-regulated [91] miR-152 Up-regulated by progesterone [48] regulation of GLUT3 expression [48] Down-regulated [90] miR-200 Promotion of EMT [84]; regulation of ZEB1/ZEB2 expression [86][87][88] Up-regulated [84] miR-203 Up-regulated in secretory phase and in implantation window [32] Promotion of EMT [84] Up-regulated [84] miR-205 Promotion of EMT [84] Up-regulated [84,90] miR-224 Promotion of EMT [84] Down-regulated [84] miR-411 Down-regulated [90] miR-429 down-regulated during implantation in mouse [45] Promotion of EMT [84] Up-regulated [84] Analysis of endometrial serous adenocarcinoma showed an up-regulation of miR-205 and down-regulation of miR-10b, miR-29b,...…”

Understanding the Complex Milieu of Epithelial-Mesenchymal Transition in Cancer Metastasis: New Insight Into the Roles of Transcription Factors

“…Consequently, loss of E-cadherin promotes the transformation of stationary epithelial cells to a migratory mesenchymal phenotype through a cascade process involving several intermediate E/M phenotypes. Apart from mutation, loss of E-cadherin may also be orchestrated by downregulation due to epigenetic or transcriptional silencing ( 12 , 13 ). All the same, mesenchymal markers such as vimentin, N-cadherin, fibronectins, smooth muscle actin, and matrix metalloproteases (MMP) also become upregulated and function concurrently with the loss of E-cadherin during the EMT program ( 14 ) ( Figure 1 ).…”