Desmocollin-2 affects the adhesive strength and cytoskeletal arrangement in esophageal squamous cell carcinoma cells

Abstract

Desmocollin-2 (DSC2), a transmembrane glycoprotein belonging to the desmosomal cadherin family, has been found to be differentially expressed in several types of cancer and to be involved in tumor progression. The tumor metastasis suppressing property of DSC2 in esophageal squamous cell carcinoma (ESCC) has been described, however, its contribution to cell cohesion in ESCC remains to be elucidated. In the present study, using RNA interference (RNAi), the expression of DSC2 was silenced in SHEEC and KYSE510 cells. Hanging drop and fragmentation assays were performed to investigate the role of DSC2 in cell-cell adhesion. Western blot analysis and confocal microscopy were used to analyze the expression and localization of cell adhesion molecules and cytoskeletal arrangement. The results demonstrated that DSC2 knock down by RNAi caused defects in cell-cell adhesion and a concomitant reduction in desmosomal protein expression and adherens junction molecule distribution. A decrease in the expression of DSC2 caused an increase in free γ-catenin levels, thus promoting its recruitment to the adherens junction complex. In addition, the RNAi-mediated inhibition of DSC2 led to keratin intermediate filament retraction and filamentous-actin cytoskeleton rearrangement. Taken together, these data support our previous findings and the proposal that DSC2 may be involved in the regulation of the invasive behavior of cells by a mechanism that controls cell-cell attachment and cytoskeleton rearrangement.

sRNA23392 packaged by Porphyromonas gingivalis outer membrane vesicles promotes oral squamous cell carcinomas migration and invasion by targeting desmocollin‐2

“…DSC2 was found to decrease in acantholytic squamous cell carcinoma of the skin (Jurčić et al, 2015). Several studies by the Wang-Kai Fang team discovered that downregulated desmocollin-2 reduces cell-cell adhesion, promotes cell aggressiveness by redistributing adherens junctions, and activating β-catenin signaling in esophageal squamous cell carcinoma (Fang et al, 2013(Fang et al, , 2014. In addition, DSC2 is involved in the transformation, and development of esophageal tumors and DSC2 expression level and intracellular localization may serve as a predictor of patient outcomes (Fang et al, 2010).…”

Regulation of intestinal epithelial intercellular adhesion and barrier function by desmosomal cadherin desmocollin-2

“…Interestingly, using a DM-Dsg 2 TS, it was reported that Dsg2 supports mechanical tension in MDCK resting cells and during cardiomyocyte contraction ( Baddam, Arsenovic et al , 2018 ). In addition, Dsc2 KD in esophageal squamous carcinoma cell lines resulted in impaired intercellular adhesion and retraction of keratin-IFs ( Fang et al , 2014 ). Furthermore, DP I/II has been reported to support tension force across intercellular junctions when external stress was applied ( Price, Cost et al , 2018 ) and by cross-linking IFs to desmosomal cadherins ( Broussard, Yang et al , 2017 ).…”

Differential Expression of Desmocollin2, Desmoglein2, and Plakophilin2 in the Progression of Esophagitis to Esophageal Adenocarcinoma

“…PKP2 may excite Top ash activity, leading to the translocation of desmosomes [33] . Another study has revealed that PKP2 can promote actin recombination and regulate the assembly of the desmosomal complex by connecting Ras homolog A and protein kinase C-dependent pathways [45] . In our study, the mRNA and protein levels of PKP2 were signi cantly upregulated in esophageal adenocarcinoma tissues compared with tissues of normal esophagus and esophagitis in rats.…”