Type VII collagen regulates expression of OATP1B3, promotes front-to-rear polarity and increases structural organisation in 3D spheroid cultures of RDEB tumour keratinocytes

Jasbani H. S. Dayal, Clare L. Cole, Celine Pourreyron, Stephen A. Watt, Yok Zuan Lim, Julio C. Salas-Alanis, Dedee F. Murrell, John A. McGrath, Bruno Stieger, Colin Jahoda, Irene M. Leigh, Andrew P. South (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    17 Citations (Scopus)

    Abstract

    Type VII collagen is the main component of anchoring fibrils, structures that are integral to basement membrane homeostasis in skin. Mutations in the gene encoding type VII collagen COL7A1 cause recessive dystrophic epidermolysis bullosa (RDEB) an inherited skin blistering condition complicated by frequent aggressive cutaneous squamous cell carcinoma (cSCC). OATP1B3, which is encoded by the gene SLCO1B3, is a member of the OATP (organic anion transporting polypeptide) superfamily responsible for transporting a wide range of endogenous and xenobiotic compounds. OATP1B3 expression is limited to the liver in healthy tissues, but is frequently detected in multiple cancer types and is reported to be associated with differing clinical outcome. The mechanism and functional significance of tumour-specific expression of OATP1B3 has yet to be determined. Here, we identify SLCO1B3 expression in tumour keratinocytes isolated from RDEB and UV-induced cSCC and demonstrate that SLCO1B3 expression and promoter activity are modulated by type VII collagen. We show that reduction of SLCO1B3 expression upon expression of full-length type VII collagen in RDEB cSCC coincides with acquisition of front-to-rear polarity and increased organisation of 3D spheroid cultures. In addition, we show that type VII collagen positively regulates the abundance of markers implicated in cellular polarity, namely ELMO2, PAR3, E-cadherin, B-catenin, ITGA6 and Ln332.
    Original languageEnglish
    Pages (from-to)740-751
    Number of pages12
    JournalJournal of Cell Science
    Volume127
    Issue number4
    DOIs
    Publication statusPublished - 15 Feb 2014

    Keywords

    • Adaptor Proteins, Signal Transducing
    • Animals
    • Cadherins
    • Carcinoma, Squamous Cell
    • Cell Adhesion Molecules
    • Cell Cycle Proteins
    • Cell Polarity
    • Coculture Techniques
    • Collagen Type VII
    • Cytoskeletal Proteins
    • Epidermolysis Bullosa Dystrophica
    • Gene Expression Regulation, Neoplastic
    • Humans
    • Integrin alpha6
    • Keratinocytes
    • Membrane Proteins
    • Mice
    • Neoplasm Transplantation
    • Organic Anion Transporters, Sodium-Independent
    • Promoter Regions, Genetic
    • Protein Transport
    • Skin Neoplasms
    • Transcription, Genetic
    • Tumor Cells, Cultured
    • Tumor Markers, Biological
    • beta Catenin

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