Figure 3.

Rap1 activation contributes to the acquisition of cancer hallmarks. Rap1 plays a diverse role in tumor initiation and progression. For instance, Rap1 activation induces tumor initiation and epithelial–mesenchymal transition (EMT) via Notch signaling. EGFR and Src/FAK may be stimulated by the activated Rap1, leading to integrin-mediated cell adhesion in cancer. The adhesion of integrins to the extracellular matrix (ECM) is an essential step for tumor cell invasion and metastasis. Src may activate MAPK/ERK to increase VEGF expression levels in the tumor cells, ultimately leading to angiogenesis. Src may also induce p130Cas and PD-L1 expression in the tumor cells. The upregulation of MMP during Rap1 activation may trigger EMT in cancer and thus enhancing invasiveness and metastasis. Therefore, Rap1 has rendered itself to be an attractive therapeutic target in cancer treatment.