title: Type VII collagen regulates expression of OATP1B3, promotes front-to-rear polarity and increases structural organisation in 3D spheroid cultures of RDEB tumour keratinocytes.
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.
authors.affiliation: Division of Cancer Research, Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK.
authors.forename: Jasbani H S
authors.initials: JH
authors.lastname: Dayal
authors.forename: Clare L
authors.initials: CL
authors.lastname: Cole
authors.forename: Celine
authors.initials: C
authors.lastname: Pourreyron
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Watt
authors.forename: Yok Zuan
authors.initials: YZ
authors.lastname: Lim
authors.forename: Julio C
authors.initials: JC
authors.lastname: Salas-Alanis
authors.forename: Dedee F
authors.initials: DF
authors.lastname: Murrell
authors.forename: John A
authors.initials: JA
authors.lastname: McGrath
authors.forename: Bruno
authors.initials: B
authors.lastname: Stieger
authors.forename: Colin
authors.initials: C
authors.lastname: Jahoda
authors.forename: Irene M
authors.initials: IM
authors.lastname: Leigh
authors.forename: Andrew P
authors.initials: AP
authors.lastname: South
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D016764:Cell Polarity; D018920:Coculture Techniques; D024143:Collagen Type VII / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D016108:Epidermolysis Bullosa Dystrophica / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D039503:Integrin alpha6 / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009368:Neoplasm Transplantation; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D021381:Protein Transport; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism; D000097794:Kalinin
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D015820:Cadherins; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; D024143:Collagen Type VII; D003598:Cytoskeletal Proteins; D039503:Integrin alpha6; D008565:Membrane Proteins; D029362:Organic Anion Transporters, Sodium-Independent; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3; D051176:beta Catenin; D000097794:Kalinin; C513384:CDH1 protein, human; C569053:COL7A1 protein, human; C495270:CTNNB1 protein, human; C486678:ELMO2 protein, human; C588002:ITGA6 protein, human; C509689:PARD3 protein, human; C421209:SLCO1B3 protein, human
keywords: OATP1B3; Polarity; Type VII collagen