Fig. 2

Signaling pathways of the CD70-CD27 axis in hematologic and solid cancers. In hematological malignancies, CD70-CD27 signaling activates the canonical Wnt, JAK/STAT, Hedgehog and TGF-ß pathways which can induce stemness/immature state. In addition, crosslinking of CD27 in a protein kinase C or ß-catenin-dependent manner and reverse signaling of CD70 were shown to induce proliferation of the malignant cells. CD70-CD27 signaling can promote survival by regulating kinases of the MEK pathway and transcription factor AP-1 and by the Wnt pathway through activation of ß-catenin. In solid tumors, CD70 signaling is associated with cancer stem cells and EMT transition via the induction of EMT-related gene expression (SOX2, CD44, Vimentin, Snail, Slug and ß-catenin) and via MAPK activation and RhoE overexpression. Furthermore, hypoxia is identified as a regulator of CD70 expression and is an important factor to promote stemness, migration and invasion of the tumor. Figure created with BioRender.com. Abbreviations; AP-1, activator protein 1; ß-cat, ß-catenin; EMT, epithelial to mesenchymal transition; JAK/STAT, Janus kinase-signal transducer and activator of transcription; MAPK, mitogen-activated protein kinase; MEK, mitogen-activated protein kinase kinase; PKC, protein kinase C; RhoE, ras homologous E; sCD27, soluble CD27; SOX2, sex determining region Y-box2; TGF-ß, transforming growth factor beta; Vim, Vimentin