Figure 4.

Overview of E-Cadherin (CDH1) involvement in OC pathogenesis from EMT to metastasis, and the main molecular and cellular functions associated with CDH1 down-expression. (A): ‘Cadherin Isoform Switching’ is the downregulation of E-cadherins (CDH1) and upregulation of N-cadherins in EMT. The adherens junctions mediated by CDH1 detach due to the downregulation of E-cadherin. This ‘Cadherin Isoform Switching’ has significantly been associated with increased migration and invasion of cancer cells, tumor stemness, metastasis, and reduced survival or higher mortality rate in cancer patients. The EMT is critical for tumor progression, drug resistance, and stemness of tumors that subsequently accelerate the initiation of metastasis. (B): The reduction or loss of CDH1 leads to the activation of an array of signaling pathways such as pro-inflammatory pathways (TGF-beta, TNF-alpha, IL-6, NfKB, p38 MAPK, ERK1/2, etc.), disruption of cell-cell junctions (Cdc42, Snail1, Snail2, Slug, E47, etc.), reorganization of cytoskeleton and cell shape (EMT), cell migration and invasion (CCND1, MMP1, MMP3, MMP9, etc.), angiogenesis (VEGF), cell proliferation (Wnt/β-catenin), inhibition of TRAIL-induced apoptosis, and cell cycle arrest (cyclin-E, Cdk2, p27KIP1, etc.) leading to cancer progression, cancer stemness, and metastasis