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T-cadherin negatively regulates the proliferation of cutaneous squamous carcinoma cells.

Mukoyama Y, Zhou S, Miyachi Y, Matsuyoshi N

Department of Dermatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

T-cadherin is a unique member of the cadherin superfamily that lacks the transmembrane and cytoplasmic domains, and is instead linked to the cell membrane via a glycosyl-phosphatidylinositol anchor. We previously reported that T-cadherin was specifically expressed on the basal keratinocytes of the epidermis, and the expression of T-cadherin was significantly reduced in invasive cutaneous squamous cell carcinoma (SCC) and in the lesional skin of psoriasis vulgaris. In this study, to obtain an insight into the role of T-cadherin in keratinocytes, we used transfection methods and examined the effect of overexpression or knockdown of T-cadherin in immortalized keratinocyte cell lines derived from SCC. T-cadherin overexpressed cells showed clearly reduced cell proliferation, but the influence of cell-cell adhesiveness and cell mobility was not detected. Using a tetracycline-regulated expression system, we also confirmed that the suppression of cell proliferation was dependent on the expression level of T-cadherin. Cell cycle analysis demonstrated that over expression of T-cadherin induced a delay in the G(2)/M phase. Our findings suggest that T-cadherin acts as an endogenous negative regulator of keratinocyte proliferation and its inactivation is the cause for keratinocyte hyperproliferation in SCC or in psoriasis vulgaris.

Published 8 April 2005 in J Invest Dermatol, 124(4): 833-8.
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Skin Cancer Books

Pathology of Vascular Skin Lesions (Current Clinical Pathology) (Current Clinical Pathology)

Pathology of Vascular Skin Lesions (Current Clinical Pathology) (Current Clinical Pathology)