EphB2 Promotes Progression of Cutaneous Squamous Cell Carcinoma

The Journal of Investigative Dermatology
Mehdi FarshchianVeli-Matti Kähäri

Abstract

Keratinocyte-derived skin cancer, cutaneous squamous cell carcinoma (cSCC), is the most common metastatic skin cancer. We have examined the role of Eph/ephrin signaling in the progression of cSCC. Analysis of the expression of EPH and EFN families in cSCC cells and normal epidermal keratinocytes revealed overexpression of EPHB2 mRNA in cSCC cells and cSCC tumors in vivo. Tumor cell-specific overexpression of EphB2 was detected in human cSCCs and in chemically induced mouse cSCCs with immunohistochemistry, whereas the expression of EphB2 was low in premalignant lesions and normal skin. Knockdown of EphB2 expression in cSCC cells suppressed growth and vascularization of cSCC xenografts in vivo and inhibited proliferation, migration, and invasion of cSCC cells in culture. EphB2 knockdown downregulated expression of genes associated with biofunctions cell viability, migration of tumor cells, and invasion of tumor cells. Among the genes most downregulated by EphB2 knockdown were MMP1 and MMP13. Moreover, activation of EphB2 signaling by ephrin-B2-Fc enhanced production of invasion proteinases matrix metalloproteinase-13 (MMP13) and MMP1, and invasion of cSCC cells. These findings provide mechanistic evidence for the role of EphB2 in...Continue Reading

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Citations

Apr 7, 2016·The Journal of Investigative Dermatology·Minna PiipponenVeli-Matti Kähäri
Sep 20, 2016·Disease Markers·Vlad VoiculescuConstantin Caruntu
Jul 15, 2016·Cell and Tissue Research·Liisa NissinenVeli-Matti Kähäri
Feb 25, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Chen ZhaoHonglei Chen
Jun 30, 2019·Molecular Carcinogenesis·Alok R KhandelwalCherie-Ann O Nathan
May 21, 2017·Oncotarget·Mehdi FarshchianVeli-Matti Kähäri
Apr 9, 2016·Oncotarget·Maria Carmela CantisaniMaria Domenica Castellone
Jun 16, 2016·Experimental Dermatology·Mehdi FarshchianVeli-Matti Kähäri
Apr 26, 2017·Annual Review of Neuroscience·Franziska DenkStephen B McMahon
Apr 29, 2020·Journal of the American Academy of Dermatology·Ashley WysongSarah T Arron
Dec 16, 2019·The American Journal of Pathology·Minna PiipponenVeli-Matti Kähäri
Jul 20, 2021·International Journal of Dermatology and Venereology·Bahar DasgebJouni Uitto

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