Significant Role of Collagen XVII And Integrin β4 in Migration and Invasion of The Less Aggressive Squamous Cell Carcinoma Cells

Abstract

Collagen XVII and integrin α6β4 have well-established roles as epithelial adhesion molecules. Their binding partner laminin 332 as well as integrin α6β4 are largely recognized to promote invasion and metastasis in various cancers, and collagen XVII is essential for the survival of colon and lung cancer stem cells. We have studied the expression of laminin γ2, collagen XVII and integrin β4 in tissue microarray samples of squamous cell carcinoma (SCC) and its precursors, actinic keratosis and Bowen’s disease. The expression of laminin γ2 was highest in SCC samples, whereas the expression of collagen XVII and integrin β4 varied greatly in SCC and its precursors. Collagen XVII and integrin β4 were also expressed in SCC cell lines. Virus-mediated RNAi knockdown of collagen XVII and integrin β4 reduced the migration of less aggressive SCC-25 cells in horizontal scratch wound healing assay. Additionally, in a 3D organotypic myoma invasion assay the loss of collagen XVII or integrin β4 suppressed equally the migration and invasion of SCC-25 cells whereas there was no effect on the most aggressive HSC-3 cells. Variable expression patterns and results in migration and invasion assays suggest that collagen XVII and integrin β4 contribute to SCC tumorigenesis.

The Role of Collagen XVII in Cancer: Squamous Cell Carcinoma and Beyond

“…Immunohistochemical analysis exhibited stronger immunoreaction of collagen XVII ectodomain in the primary SCC tumor and associated metastases (51). This is similarly noted in atypical keratinocytes of actinic keratoses and SCC in situ (51,52). Viral mediated RNA interference knockdown of collagen XVII and/or β4 disrupted the migration and invasion of less aggressive SCC cells (52).…”

“…Viral mediated RNA interference knockdown of collagen XVII and/or β4 disrupted the migration and invasion of less aggressive SCC cells (52). Of note, no impact was observed on HSC-3, a highly invasive cell with upregulated collagen XVII (52).…”

“…Immunohistochemical visualization has demonstrated that mature type hemidesmosome 1 (collagen XVII + integrin α6β4; HD-1) can be found in the human pancreatic ductal epithelium, with subsequent disassembly during pancreatic carcinogenesis (14). The HD-1 breakdown is part of the phosphoinositide 3kinase dependent induction of matrix-metalloprotease 9 (MMP-9), which cleaves collagen XVII and enables integrin α6β4 to promote cell migration and invasion (14,52).…”

Construction and analysis of the lncRNA-miRNA-mRNA network based on competitive endogenous RNA reveal functional lncRNAs in oral cancer

“…Functional enrichment analysis has been used to reveal biological functions of mRNAs, ceRNA counterparts of lncRNA (39). As a result, three differentially enrichment GO terms(collagen binding (40), extracellular matrix binding (29) and cell adhesion molecule binding(31))…”

Invasion and migration of MDA‐MB‐231 cells are inhibited by block of AhR and NFAT: role of AhR/NFAT1/β4 integrin signaling

“…Besides, it has been reported that AhR expression silencing or knockdown results in higher migration and invasion (Lee et al, ; Rico‐Leo, Alvarez‐Barrientos, & Fernandez‐Salguero, ). Furthermore, downregulation of β4 integrin inhibited cell invasion and migration in different cancer cells (Moilanen et al, ; Zhang et al, ). Therefore, one can conclude that lower AhR expression and elevated β4 integrin level can play a role in the invasion/migration process.…”