AI Article Synopsis
- Cadherins are important proteins involved in cell adhesion and play significant roles in cell growth and development, particularly in muscle cells.
- The study examines the presence of R-cadherin in rhabdomyosarcomas (RMS) and its absence in normal muscle cells, finding that R-cadherin inhibits muscle cell differentiation and promotes cancerous behaviors such as increased cell movement and tumor growth.
- The research suggests that R-cadherin's effects are linked to its activation of Rac1, a signaling molecule, making it a potential target for new treatments for RMS.
Article Abstract
Cadherins are transmembrane glycoproteins that mediate Ca(2+)-dependent homophilic cell-cell adhesion and play a crucial role in proliferation, differentiation, and cell transformation. The goal of this study was to understand why R-cadherin is found in rhabdomyosarcomas (RMS), tumors of skeletal muscle origin, whereas it is absent in normal myoblasts. We show that R-cadherin expression in C2C12 myoblasts causes inhibition of myogenesis induction and impairment of cell cycle exit when cells are cultured in differentiation medium. Furthermore, R-cadherin expression elicits myoblast transformation, as shown by anchorage-independent growth in soft agar in vivo tumor formation assays and increased cell motility. In contrast, inhibition of R-cadherin expression using RNA interference hinders growth of RD cell line in soft agar and its tumorigenicity in mice. The analysis of the nature of R-cadherin-mediated signals shows that R-cadherin-dependent adhesion increases Rac1 activity. Dominant-negative forms of Rac1 inhibit R-cadherin-mediated signaling and transformation. In addition, expression of R-cadherin results in perturbed function of endogenous N-cadherin and M-cadherin. Together, these data suggest that R-cadherin expression inhibits myogenesis and induces myoblast transformation through Rac1 activation. Therefore, the properties of R-cadherin make it an attractive target for therapeutic intervention in RMS.
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| http://dx.doi.org/10.1158/0008-5472.CAN-08-0196 | DOI Listing |
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