The ERBB-STAT3 Axis Drives Tasmanian Devil Facial Tumor Disease

ABSTRACT: The marsupial Tasmanian devil (Sarcophilus harrisii) faces extinction due to transmissible devil facial tumor disease (DFTD). To unveil the culprit molecular underpinnings, we designed an approach that combines sensitivity to drugs with an integrated systems-biology characterization. Sensitivity to inhibitors of the ERBB family of receptor tyrosine kinases correlated with their overexpression, suggesting a causative link. Proteomic and DNA methylation analyses revealed tumor-specific signatures linked to oncogenic signaling hubs including evolutionary conserved STAT3. Indeed, inhibition of ERBB blocked phosphorylation of STAT3 and arrested cancer cells. Blockade of ERBB signaling prevented tumor growth in a xenograft model and resulted in recovery of MHC-I gene expression. This link between the hyperactive ERBB-STAT3 axis and decreased MHC-I mediated tumor immunosurveillance provides mechanistic insights into horizontal transmissibility and lets us propose a dual chemo-immunotherapeutic strategy to save Tasmanian devils from DFTD.

OTHER RELATED OMICS DATASETS IN: GSE108107 GSE108160

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Sarcophilus Harrisii

TISSUE(S): Spleen, Skin

SUBMITTER: Alexandra Popa  

LAB HEAD: Dr Andreas Bergthaler

PROVIDER: PXD009283 | Pride | 2019-01-18

REPOSITORIES: Pride