Mutant p53 induces a hypoxia transcriptional program in gastric and esophageal adenocarcinoma

• DOI: 10.1172/jci.insight.128439
• Publication Date: 2019-08-07T15:00:57Z
• Authors: Nilay Sethi; Osamu Kikuchi; James McFarland; Yanxi Zhang; Max Chung; Nicholas Kafker; Mirazul Islam; Benjamin Lampson; Abhishek Chakraborty; William G. Kaelin; Adam J. Bass
• Keywords: Hypoxia

Despite the propensity for gastric and esophageal adenocarcinomas to select recurrent missense mutations in TP53, precise functional consequence of these remains unclear. Here we report that endogenous mRNA protein levels mutant p53 were elevated cell lines patients with cancer. Functional studies showed was sufficient, but not necessary, enhancing primary tumor growth vivo. Unbiased genome-wide transcriptome analysis revealed hypoxia signaling induced by 2 cancer lines. Using real-time vivo imaging, confirmed reporter activity during initiation xenografts. Unlike HIF co-factor ARNT, HIF1α required These findings elucidate contribution gastroesophageal malignancy indicate rather than itself may serve as a therapeutic vulnerability deadly set cancers.