T-cadherin negatively regulates the proliferation of cutaneous squamous carcinoma cells.
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.
Mukoyama
Yohei
Y
Department of Dermatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Zhou
Shuxia
S
Miyachi
Yoshiki
Y
Matsuyoshi
Norihisa
N
D015820:Cadherins / Q000235:genetics / Q000502:physiology*; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000503:physiopathology*; D002449:Cell Aggregation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D015536:Down-Regulation; D016195:G2 Phase / Q000502:physiology; D015870:Gene Expression; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology; D012878:Skin Neoplasms / Q000473:pathology / Q000503:physiopathology*
D015820:Cadherins; C099972:H-cadherin