T-cadherin enhances cell-matrix adhesiveness by regulating beta1 integrin trafficking in cutaneous squamous carcinoma cells.

Abstract

T-cadherin is a glycosyl-phosphatidylinositol (GPI) anchored cadherin molecule. We previously reported that T-cadherin is normally expressed on the basal keratinocytes of the epidermis and is down-regulated in cutaneous squamous cell carcinoma (SCC). We found that expression of T-cadherin in cutaneous squamous carcinoma cells regulated level of surface beta1 integrin, which functioned as extracellular matrix (ECM) receptor. Involvement of T-cadherin in beta1 integrin trafficking was studied using three different stable cell lines with cytomegalovirus (CMV)-driven over-expression, tetracycline (Tet)-inducible expression and RNAi-mediated suppressed expression of T-cadherin. Pulse-chase analysis using a cholesterol-depleting reagent and a tyrosine kinase inhibitor showed that beta1 integrin mainly internalized via caveolae. Over-expression of T-cadherin suppressed the internalization of both beta1 integrin and cholera toxin (CTX), a marker of caveolae-mediated endocytosis. By Western blot analysis of tyrosine-kinase target molecules, we demonstrated a reduced level of EGF receptor (EGFR)-phosphorylation in T-cadherin over-expressing cells. In addition, studies using EGF and EGFR specific inhibitors revealed that EGFR activation stimulated beta1 integrin internalization. Taking these results together, T-cadherin may modulate cell-matrix adhesion in basal keratinocytes as well as invasive potency in SCC by regulating surface level of beta1 integrin.

• Authors: Yohei Mukoyama, Atsushi Utani, Seiya Matsui, Shuxia Zhou, Yoshiki Miyachi, Norihisa Matsuyoshi
• Journal: Genes to cells : devoted to molecular & cellular mechanisms (Genes Cells) Vol. 12 Issue 6 Pg. 787-96 (Jun 2007) ISSN: 1356-9597 [Print] England
• PMID: 17573778 (Publication Type: Journal Article)

Chemical References

• Cadherins
• Glycosylphosphatidylinositols
• H-cadherin
• Integrin beta1
• ErbB Receptors

Topics

• Cadherins (biosynthesis, metabolism)
• Carcinoma, Squamous Cell (metabolism)
• Cell Adhesion
• Cell Line
• ErbB Receptors (metabolism)
• Extracellular Matrix (metabolism)
• Gene Expression Regulation
• Gene Expression Regulation, Neoplastic
• Glycosylphosphatidylinositols (chemistry)
• Humans
• Integrin beta1 (metabolism)
• Keratinocytes (metabolism)
• RNA Interference
• Signal Transduction
• Skin Neoplasms (metabolism)