| First Author | Lan L | Year | 2026 |
| Journal | Cell Rep | Volume | 45 |
| Issue | 2 | Pages | 116909 |
| PubMed ID | 41581147 | Mgi Jnum | J:379667 |
| Mgi Id | MGI:8289350 | Doi | 10.1016/j.celrep.2025.116909 |
| Citation | Lan L, et al. (2026) A Jagged1-regulated hybrid-EMT state identifies pancreatic cancer stem cells. Cell Rep 45(2):116909 |
| abstractText | Pancreatic ductal adenocarcinoma (PDAC) shows great cellular heterogeneity, with pronounced epithelial and mesenchymal cancer cell populations. We previously identified a PDAC subpopulation, marked by the tetraspanin CD9, which is capable of initiating PDAC and giving rise to PDAC heterogeneity. Here, we characterize a subset of CD9-high (CD9(hi)) tumor-initiating cells (TICs) with hybrid epithelial-mesenchymal transition (EMT) features, which show increased cancer stem cell properties, as evidenced by increased capacity to form organoids and generate epithelial and mesenchymal tumor cell progeny. Depletion of hybrid-EMT CD9(hi) cells leads to a gradual collapse of organoid formation and tumorigenic capability, suggesting that CD9(hi) TICs are required for long-term organoid formation and tumorigenicity. Hybrid-EMT CD9(hi) TICs upregulate the Notch ligand Jagged1, and Jag1 depletion or Notch inhibition impairs TIC self-renewal and PDAC cell differentiation. Conversely, Jag1 overexpression augments TIC self-renewal. Thus, Jagged1-mediated Notch signaling controls a hybrid-EMT state that is a defining feature of TICs in PDAC. |
