Fig. 8: Genetically-defined oncogenic and tumor suppressive pathway alteration in normal oral epithelial progenitor cells defines tumor initiating events.
From: YAP-driven malignant reprogramming of oral epithelial stem cells at single cell resolution
Employing spatiotemporally controlled constitutive YAP activation and HPVE6-E7-mediated tumor suppressor inhibition in oral epithelial progenitor cells, we illuminate processes underlying oncogenic reprogramming leading to tumor initiation. Tumor initiating events included YAP-mediated transcription of factors driving EGFR signaling resulting in mTOR activation. Tumor initiating transcriptional programs encompassed aberrant cell cycle activation, hypoxia response, inflammatory response, partial epithelial to mesenchymal (pEMT), and extracellular matrix (ECM) remodeling. These programs endowed tumor cells with intrinsic invasive potential as well as the expression of chemokines resulting in recruitment of MMP8 and MMP9-producing myeloid-derived suppressor cells (MDSC) to the invasive front further enabling tumor invasion. Created in BioRender. https://BioRender.com/a88s502.
