Brooke A Brown, Paul J Myers, Sara J Adair, Jason R Pitarresi, Shiv K Sah-Teli, Logan A Campbell, William S Hart, Michelle C Barbeau, Kelsey Leong, Nicholas Seyler, William Kane, Kyoung Eun Lee, Edward Stelow, Marieke Jones, M Celeste Simon, Peppi Koivunen, Todd W Bauer, Ben Z Stanger, Matthew J Lazzara
The tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC) plays a key role in tumor progression and response to therapy. The dense PDAC stroma causes hypovascularity, which leads to hypoxia. Here, we showed that hypoxia drives long-lasting epithelial-mesenchymal transition (EMT) in PDAC primarily through a positive-feedback histone methylation-MAPK signaling axis. Transformed cells preferentially underwent EMT in hypoxic tumor regions in multiple model systems. Hypoxia drove a cell-autonomous EMT in PDAC cells which, unlike EMT in response to growth factors, could last for weeks...
March 12, 2024: Cancer Research