| First Author | Huang YH | Year | 2020 |
| Journal | Cancer Discov | Volume | 10 |
| Issue | 1 | Pages | 142-157 |
| PubMed ID | 31582374 | Mgi Jnum | J:283662 |
| Mgi Id | MGI:6386900 | Doi | 10.1158/2159-8290.CD-19-0529 |
| Citation | Huang YH, et al. (2020) ID1 Mediates Escape from TGFbeta Tumor Suppression in Pancreatic Cancer. Cancer Discov 10(1):142-157 |
| abstractText | TGFbeta is an important tumor suppressor in pancreatic ductal adenocarcinoma (PDA), yet inactivation of TGFbeta pathway components occurs in only half of PDA cases. TGFbeta cooperates with oncogenic RAS signaling to trigger epithelial-to-mesenchymal transition (EMT) in premalignant pancreatic epithelial progenitors, which is coupled to apoptosis owing to an imbalance of SOX4 and KLF5 transcription factors. We report that PDAs that develop with the TGFbeta pathway intact avert this apoptotic effect via ID1. ID1 family members are expressed in PDA progenitor cells and encode components of a set of core transcriptional regulators shared by PDAs. PDA progression selects against TGFbeta-mediated repression of ID1. The sustained expression of ID1 uncouples EMT from apoptosis in PDA progenitors. AKT signaling and mechanisms linked to low-frequency genetic events converge on ID1 to preserve its expression in PDA. Our results identify ID1 as a crucial node and potential therapeutic target in PDA. SIGNIFICANCE: Half of PDAs escape TGFbeta-induced tumor suppression without inactivating the TGFbeta pathway. We report that ID1 expression is selected for in PDAs and that ID1 uncouples TGFbeta-induced EMT from apoptosis. ID1 thus emerges as a crucial regulatory node and a target of interest in PDA.This article is highlighted in the In This Issue feature, p. 1. |
