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

[dystrophic epidermolysis bullosa]

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 COL 7 A 1 cause recessive dystrophic epidermolysis bullosa (RDEB ) an inherited skin blistering condition complicated by frequent aggressive cutaneous squamous cell carcinoma (cSCC ). OATP 1 B 3 , which is encoded by the gene SLCO 1 B 3 , is a member of the OATP (organic anion transporting polypeptide ) superfamily responsible for transporting a wide range of endogenous and xenobiotic compounds . OATP 1 B 3 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 OATP 1 B 3 has yet to be determined . Here , we identify SLCO 1 B 3 expression in tumour keratinocytes isolated from RDEB and UV-induced cSCC and demonstrate that SLCO 1 B 3 expression and promoter activity are modulated by type VII collagen . We show that reduction of SLCO 1 B 3 expression upon expression of full-length type VII collagen in RDEB cSCC coincides with acquisition of front-to -rear polarity and increased organisation of 3 D spheroid cultures . In addition , we show that type VII collagen positively regulates the abundance of markers implicated in cellular polarity , namely ELMO 2 , PAR 3 , E -cadherin , B-catenin , ITGA 6 and Ln 332 .

Diseases
Validation

Diseases presenting "recessive dystrophic epidermolysis bullosa" symptom

child syndrome

dystrophic epidermolysis bullosa

junctional epidermolysis bullosa

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