title: Expression of claudin-11 by tumor cells in cutaneous squamous cell carcinoma is dependent on the activity of p38δ.
abstract: The incidence of cutaneous squamous cell carcinoma (cSCC) is rapidly increasing, and the prognosis of patients with metastatic disease is poor. There is an emerging need to identify molecular markers for predicting aggressive behaviour of cSCC. Here, we have examined the role of tight junction (TJ) components in the progression of cSCC. The expression pattern of mRNAs for TJ components was determined with RNA sequencing and oligonucleotide array-based expression analysis from cSCC cell lines (n=8) and normal human epidermal keratinocytes (NHEK, n=5). The expression of CLDN11 was specifically elevated in primary cSCC cell lines (n=5), but low or absent in metastatic cSCC cell lines (n=3) and NHEKs. Claudin-11 was detected in cell-cell contacts of primary cSCC cells in culture by indirect immunofluorescence analysis. Analysis of a large panel of tissue samples from sporadic UV-induced cSCC (n=65), cSCC in situ (n=56), actinic keratoses (n=31), seborrhoeic keratoses (n=7) and normal skin (n=16) by immunohistochemistry showed specific staining for claudin-11 in intercellular junctions of keratinizing tumor cells in well and moderately differentiated cSCCs, whereas no staining for claudin-11 was detected in poorly differentiated tumors. The expression of claudin-11 in cSCC cells was dependent on the activity of p38δ MAPK and knock-down of claudin-11 enhanced cSCC cell invasion. These findings provide evidence for the role of claudin-11 in regulation of cSCC invasion and suggest loss of claudin-11 expression in tumor cells as a biomarker for advanced stage of cSCC.
authors.affiliation: Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland.|MediCity Research Laboratory, University of Turku, Turku, Finland.
authors.forename: Liisa
authors.initials: L
authors.lastname: Nissinen
authors.affiliation: Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland.|MediCity Research Laboratory, University of Turku, Turku, Finland.
authors.forename: Elina
authors.initials: E
authors.lastname: Siljamäki
authors.affiliation: Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland.|MediCity Research Laboratory, University of Turku, Turku, Finland.
authors.forename: Pilvi
authors.initials: P
authors.lastname: Riihilä
authors.affiliation: Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland.|MediCity Research Laboratory, University of Turku, Turku, Finland.
authors.forename: Minna
authors.initials: M
authors.lastname: Piipponen
authors.affiliation: Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland.|MediCity Research Laboratory, University of Turku, Turku, Finland.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Farshchian
authors.affiliation: Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland.|MediCity Research Laboratory, University of Turku, Turku, Finland.
authors.forename: Atte
authors.initials: A
authors.lastname: Kivisaari
authors.affiliation: Department of Pathology, University of Turku and Turku University Hospital, Turku, Finland.
authors.forename: Markku
authors.initials: M
authors.lastname: Kallajoki
authors.affiliation: Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland.
authors.forename: Laura
authors.initials: L
authors.lastname: Raiko
authors.affiliation: Department of Cell Biology and Anatomy, University of Turku, Turku, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Peltonen
authors.affiliation: Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland.
authors.forename: Sirkku
authors.initials: S
authors.lastname: Peltonen
authors.affiliation: Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland.|MediCity Research Laboratory, University of Turku, Turku, Finland.
authors.forename: Veli-Matti
authors.initials: VM
authors.lastname: Kähäri
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002460:Cell Line; D057167:Claudins / Q000378:metabolism*; D006801:Humans; D048292:Mitogen-Activated Protein Kinase 13 / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C120453:CLDN11 protein, human; D057167:Claudins; D048292:Mitogen-Activated Protein Kinase 13
keywords: claudin; invasion; p38; skin cancer; tight junction