The emerging role of human transmembrane RGD-based counter-receptors of integrins in health and disease
Most of the canonical Arg-Gly-Asp (RGD)-containing integrin ligands are extracellular matrix proteins, such as fibronectin, vitronectin and fibrinogen, which regulate cell-ECM adhesion processes. However, during the last years, several reports have demonstrated the existence of non-canonical RGD-con...
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| Main Authors: | , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
December 2025
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| In: |
Cellular & molecular biology letters
Year: 2025, Volume: 30, Pages: 1-40 |
| ISSN: | 1689-1392 |
| DOI: | 10.1186/s11658-025-00787-7 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1186/s11658-025-00787-7
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| Author Notes: | Carlos Cabañas, Elisa Rossi, Ruben A. Bartolomé, Kai Doberstein, Peter Altevogt, J. Ignacio Casal and Carmelo Bernabeu |
| Summary: | Most of the canonical Arg-Gly-Asp (RGD)-containing integrin ligands are extracellular matrix proteins, such as fibronectin, vitronectin and fibrinogen, which regulate cell-ECM adhesion processes. However, during the last years, several reports have demonstrated the existence of non-canonical RGD-containing integrin ligands that are cell surface transmembrane proteins. At variance with the canonical extracellular matrix integrin ligands, the RGD-containing cell surface integrin ligands are involved in cell-cell adhesion processes and function as “integrin counter-receptors”. We propose in this review grouping these transmembrane proteins, which include endoglin, cadherin-5, cadherin-6, cadherin-17, ADAM15, and L1CAM, under the newly coined acronym RGD-ICRs (RGD-containing Integrin Counter-Receptors). We present and discuss the structure of RGD-ICRs, their RGD-based interactions with integrins, the specific signaling pathways triggered in different cell types, as well as their pathophysiological involvement. It can be postulated that RGD-ICRs constitute an emerging group of non-canonical RGD-based integrin counter-receptors. In spite of being encoded by different and independent genes and involved in different pathophysiological processes, all of them appear to have undergone a strong evolutionary convergence in order to acquire the same functional capacity to bind integrins via the RGD motif. Importantly, these RGD-ICRs are also emerging as novel biomarkers and therapeutic targets, with promising clinical potential in a wide array of pathologies. |
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| Item Description: | Online veröffentlicht: 2. Oktober 2025 Gesehen am 18.12.2025 |
| Physical Description: | Online Resource |
| ISSN: | 1689-1392 |
| DOI: | 10.1186/s11658-025-00787-7 |