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

Research output: Contribution to journalArticle

14 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. © 2014. Published by The Company of Biologists Ltd.
Original languageEnglish
Pages (from-to)740-751
Number of pages12
JournalJournal of Cell Science
DOIs
Publication statusPublished - 15 Feb 2014
Externally publishedYes

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Collagen Type VII
Epidermolysis Bullosa Dystrophica
Keratinocytes
Skin
Squamous Cell Carcinoma
Neoplasms
Catenins
Xenobiotics
Cadherins
Basement Membrane
Genes
Anions
Homeostasis
Peptides
Mutation
Liver

Cite this

Dayal, Jasbani H.S. ; Cole, Clare L. ; Pourreyron, Celine ; Watt, Stephen A. ; Lim, Yok Zuan ; Salas-Alanis, Julio C. ; Murrell, Dedee F. ; McGrath, John A. ; Stieger, Bruno ; Jahoda, Colin ; Leigh, Irene M. ; South, Andrew P. / Type VII collagen regulates expression of OATP1B3, promotes front-to-rear polarity and increases structural organisation in 3D spheroid cultures of RDEB tumour keratinocytes. In: Journal of Cell Science. 2014 ; pp. 740-751.
@article{7ee8e3a56d1644fb9ae7a157e9943995,
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. {\circledC} 2014. Published by The Company of Biologists Ltd.",
author = "Dayal, {Jasbani H.S.} and Cole, {Clare L.} and Celine Pourreyron and Watt, {Stephen A.} and Lim, {Yok Zuan} and Salas-Alanis, {Julio C.} and Murrell, {Dedee F.} and McGrath, {John A.} and Bruno Stieger and Colin Jahoda and Leigh, {Irene M.} and South, {Andrew P.}",
year = "2014",
month = "2",
day = "15",
doi = "10.1242/jcs.128454",
language = "English",
pages = "740--751",
journal = "Journal of Cell Science",
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Dayal, JHS, Cole, CL, Pourreyron, C, Watt, SA, Lim, YZ, Salas-Alanis, JC, Murrell, DF, McGrath, JA, Stieger, B, Jahoda, C, Leigh, IM & South, AP 2014, 'Type VII collagen regulates expression of OATP1B3, promotes front-to-rear polarity and increases structural organisation in 3D spheroid cultures of RDEB tumour keratinocytes', Journal of Cell Science, pp. 740-751. https://doi.org/10.1242/jcs.128454

Type VII collagen regulates expression of OATP1B3, promotes front-to-rear polarity and increases structural organisation in 3D spheroid cultures of RDEB tumour keratinocytes. / Dayal, Jasbani H.S.; Cole, Clare L.; Pourreyron, Celine; Watt, Stephen A.; Lim, Yok Zuan; Salas-Alanis, Julio C.; Murrell, Dedee F.; McGrath, John A.; Stieger, Bruno; Jahoda, Colin; Leigh, Irene M.; South, Andrew P.

In: Journal of Cell Science, 15.02.2014, p. 740-751.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Type VII collagen regulates expression of OATP1B3, promotes front-to-rear polarity and increases structural organisation in 3D spheroid cultures of RDEB tumour keratinocytes

AU - Dayal, Jasbani H.S.

AU - Cole, Clare L.

AU - Pourreyron, Celine

AU - Watt, Stephen A.

AU - Lim, Yok Zuan

AU - Salas-Alanis, Julio C.

AU - Murrell, Dedee F.

AU - McGrath, John A.

AU - Stieger, Bruno

AU - Jahoda, Colin

AU - Leigh, Irene M.

AU - South, Andrew P.

PY - 2014/2/15

Y1 - 2014/2/15

N2 - 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. © 2014. Published by The Company of Biologists Ltd.

AB - 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. © 2014. Published by The Company of Biologists Ltd.

U2 - 10.1242/jcs.128454

DO - 10.1242/jcs.128454

M3 - Article

SP - 740

EP - 751

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

ER -