Epithelial Protein Lost in Neoplasm, EPLIN, the Cellular and Molecular Prospects in Cancers

Figure 1. Schematic structure of EPLIN. Structural information is adapted from [5,6] and figure is designed and created by using Adobe Illustrator 2021Version 25.2.1 (Adobe Inc., San Jose, CA, USA).

Figure 2. A. Role of EPLIN in apical extrusion. Rab5 allows disruption of the connection between the cadherin–catenin complex and EPLIN, allowing EPLIN to interact with paxillin and plectin to recruit/activate Cav-1, PKA and Myosin II, and acetylate tubulin through paxillin’s regulation of HDAC6 activity. Hence, promoting apical elimination when Ras-transformed cells are surrounded by normal cells. B. EPLIN prospective pathways in epithelium. EPLIN stabilises AJs and actin dynamics by binding to the cadherin–catenin complex and actin directly. PDGF/EGF could induce phosphorylation of EPLIN via ERK signalling pathways and results in disorganisation of AJs and interruption of actin dynamics, which further upregulates expression/translocation of β-catenin and ZEB1, diminishes expression of E-cadherin leading to activation of the β-catenin/Wnt pathway and promotion of EMT, further impacting cellular functions. This phosphorylation of EPLIN can be counteracted by hCDC14A. DNp73 induces downregulation of EPLIN, which allows IGF1R to interact with its ligand, then phosphorylate AKT and STAT3, which increases expression of Slug and decreases expression of E-cadherin, to contribute to promotion of…

Figure 3. EPLIN’s role in endothelium. EPLIN sustains cell junctions in ECs by linking to VE-cadherin via α-catenin. Downregulation of EPLIN could be induced by upregulation of miR-93-5p, which may subsequently lead to translocation of vinculin away from cell junctions. Downregulation of EPLIN also results in promotion of cellular migration and supports angiogenesis. EPLIN-α has been reported to locate at JAIL and cLP and to regulate protrusion progression via the Arp2/3 complex, whilst EPLIN-β mainly locates at stress fibres to maintain its stability. Icons were obtained from SMART-Servier Medical ART (https://smart.servier.com, accessed on 18 April 2021) and graphics of pathways were designed and created using Adobe Illustrator 2021 Version 25.2.1 (Adobe Inc., San Jose, CA, USA).