Isabel, Paola, Cabrera, Medina, Scales, Michael, Steele, Nina, Franks, Nicole, Dear, Hannah, Biffi, Giulia, Tuveson, David, Pasca di Magliano, Marina, Allen, Benjamin (November 2025) Investigating the roles of GLI transcription factors in the pancreatic cancer microenvironment. In: UNSPECIFIED.
Abstract
Pancreatic ductal adenocarcinoma (PDA) remains a difficult cancer to treat due to an extensive and complex tumor microenvironment. In particular, intercellular signaling between tumor cells, fibroblasts and immune cells is a key contributor to pancreatic tumor growth. One of these signals, the Hedgehog (HH) pathway, is a known feature of PDA. Pancreatic tumor cells secrete HH ligands, which signal in a paracrine fashion to fibroblasts in the tumor microenvironment. Notably, the role of HH signaling is complicated, with reports suggesting both tumor-promoting and tumor- restraining functions in pancreatic cancer. GLI proteins (GLI1-3) are the transcriptional effectors of the HH pathway; their contribution to pancreatic tumor growth is equally complex. This study seeks to investigate the contribution of GLI1-3 in PDA progression. Our lab has demonstrated that Gli1-3 are expressed in pancreatic fibroblasts and that all three Glis functionally contribute to pancreatic cancer progression through effects on immune cell infiltration. To further explore the mechanisms of GLI function, we have generated a novel mouse model carrying endogenous, epitope-tagged Gli alleles (Gli1FLAG/FLAG;Gli2HA/HA;Gli3V5/V5). This model will allow us to define GLI protein processing as well as the identification of target genes to elucidate the contribution of GLI-driven transcriptional programs that regulate tumor immune infiltration in PDA.
| Item Type: | Conference or Workshop Item (Paper) |
|---|---|
| Subjects: | diseases & disorders > cancer diseases & disorders diseases & disorders > cancer > cancer types > pancreatic cancer diseases & disorders > cancer > cancer types |
| CSHL Authors: | |
| Communities: | CSHL labs > Tuveson lab |
| SWORD Depositor: | CSHL Elements |
| Depositing User: | CSHL Elements |
| Date: | 20 November 2025 |
| Date Deposited: | 22 Dec 2025 12:57 |
| Last Modified: | 22 Dec 2025 12:57 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/42044 |
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