Transforming growth factor beta receptor type 2-CD44 antigen complex (TGFBR2-CD44 complex)

The Transforming growth factor beta receptor type 2 (TGFBR2) complexed with CD44 in lipid rafts is a functional signaling unit that plays a critical role in modulating cellular responses to TGFβ ligands (UniProt P37173, P16070). CD44, a cell-surface glycoprotein, functions as a co-receptor that facilitates the assembly and activation of the TGFβ receptor complex within specialized membrane microdomains known as lipid rafts (PMID: 11544254). This localization is essential for the efficient induction of the epithelial-mesenchymal transition (EMT), a process by which epithelial cells acquire invasive mesenchymal properties (PMID: 22491014). In oncogenic contexts, the CD44-TGFBR2 complex promotes tumor progression, metastasis, and the maintenance of cancer stem cell niches by activating both Smad-dependent and non-canonical signaling pathways (PMID: 25131274). Targeting this complex involves the use of TGFBR2 kinase inhibitors like Galunisertib or CD44-specific antibodies to disrupt the pro-tumorigenic signaling cascade (ClinicalTrials.gov NCT01246986). However, therapeutic intervention is complicated by the dual role of TGFβ as both a tumor suppressor in early stages and a promoter in late-stage disease, as well as potential toxicities related to systemic TGFβ inhibition, such as cardiovascular issues (PMID: 28103464).

Other names

TGF-beta receptor II/CD44 complexCD44-TGFBR2 signaling moduleTGFBR2-CD44-lipid raft assemblyCD44-TGF-beta receptor complex

Inhibition of TGFBR2 serine/threonine kinase activity, blockade of TGF-beta ligand binding, or disruption of CD44-mediated co-receptor assembly within membrane microdomains.