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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jul 05, 2022 |
| Title |
Combinatorial Gli activity directs immune infiltration and tumor growth in pancreatic cancer |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Proper Hedgehog (HH) signaling is essential for normal embryonic and postnatal development, while de-regulated HH signaling drives numerous pediatric and adult cancers. In pancreatic cancer, paracrine HH signaling from tumor cells to fibroblasts contributes to tumor progression. However, the role of HH signaling in pancreatic cancer remains controversial, with both tumor-promoting and tumor-restraining functions reported. Notably, the GLI family of transcription factors (GLI1, GLI2, GLI3), key downstream effectors of HH signaling, remain poorly understood in pancreatic cancer. In this study we investigated the individual and combined roles of GLI1-3 in pancreatic cancer progression. Inducible, fibroblast-specific deletion of Gli2 and Gli3 in a mouse model of pancreatic cancer progression reduces collagen deposition and decreases immunosuppressive myeloid cell infiltration. Further, Gli2 and Gli3 deletion leads to an increase in T cells during PanIN stages and an increase in NK cells in implanted tumors, which in turn suppresses tumor growth. Surprisingly, combined loss of all three Glis leads to a widespread loss of acinar cells, an increase in macrophage infiltration, and an increase in tumor growth. Together, these data indicate that a baseline level of Gli is necessary to maintain proper balance of cell types in the pancreas, and the coordinated activity of GLI1-3 directs the fibroinflammatory response in pancreatic cancer.
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| Overall design |
Three independent biological replicates of wildtype and Gli2/Gli3 knock-out pancreatic fibroblasts.
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| Contributor(s) |
Scales MK, Velez-Delgado A, Steele NG, Schrader HE, Stabnick AM, Yan W, Mercado Soto NM, Nwosu ZC, Johnson C, Zhang Y, Salas-Escabillas DJ, Menjivar RE, Maurer HC, Olive KP, Pasca di Magliano M, Allen BL |
| Citation(s) |
35867772 |
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| Submission date |
Oct 12, 2021 |
| Last update date |
Jul 27, 2022 |
| Contact name |
Michael Kemper Scales |
| Organization name |
University of Michigan
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| Department |
Cell and Developmental Biology
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| Street address |
109 Zina Pitcher Place
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| City |
Ann Arbor |
| State/province |
MI |
| ZIP/Postal code |
48109 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA770661 |
| SRA |
SRP341043 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE185748_RawCounts_matrix.txt.gz |
480.2 Kb |
(ftp)(http) |
TXT |
| GSE185748_Voom_LogCPM.txt.gz |
774.9 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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