Fig. 2
From: Targeting CD24 as a novel immunotherapy for solid cancers
Schematic representation of the main CD24-mediated signaling pathways, Wnt/β-catenin, MAPK, PI3K/Akt/mTOR, Notch and Hedgehog. A The canonical Wnt signaling pathway is initiated when Wnt binds to a cell-surface receptor complex, consisting of the seven-pass transmembrane FZD and the single-pass LRP 5or 6. This leads to disassociation of the β-catenin degradation complex APC/Axin/GSK-3β, as well as β-catenin stabilization. Subsequently, the accumulated β-catenin is translocated into the nucleus, where it stimulates the transcription of TCF/LEF target genes. B Ras combines with Raf and mobilizes the inactive protein from the cytoplasm recruiting the Raf kinases to the plasma membrane. Once the Ras-Raf complex is translocated to the cell membrane, Ras activates the serine/threonine kinase function of Raf isoforms. Numerous effectors signals converge on RAF, activated RAF phosphorylates MEK in the cytoplasm, which in turn phosphorylates ERKs that translocate to the nucleus where they phosphorylate and regulate various nuclear and cytoplasmic substrates involved in diverse cellular responses. C The PI3K/Akt pathway is the upstream of mTOR, and the activation of Akt phosphorylates corresponding enzymes and kinases. In addition, mTOR regulates the promoter of downstream gene through STAT3 phosphorylation. D The transmembrane receptor Notch interacts with ligand Delta. Then Notch receptors are cleaved by γ-secretase, releasing NCID and subsequently activating Notch signaling. NCID is then translocated to the nucleus where it induces gene transcription by interacting with other co-factors. E The Hh ligands inhibit Hh pathway after binding to the twelve transmembrane protein Ptch1, which in turns interacts with the seven transmembrane protein Smo that releases five-zinc finger transcription factor GLI1/2 from a large protein complex. Abbreviations: LRP: low-density lipoprotein; FZD: frizzled; NCID: Notch intracellular domains; Hh, Hedgehog; Ptch1: Patched1; STAT3, signal transducer and activator of transcription 3; PI3K, phosphatidylinositol-3-kinase; MAPK, mitogen-activated protein kinase; Smo: Smoothened