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| Status |
Public on Nov 10, 2023 |
| Title |
Transcriptomic analysis of human dermal fibroblasts overexpressing ANKRD1. |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Stromal cell senescence plays a crucial role in activating cancer-associated fibroblasts (CAFs). The Androgen receptor (AR) function oversees cellular senescence and CAF activation. Here, we identify the mesenchymal-specific transcriptional coregulator ANKRD1 as a key driver of CAF conversion. ANKRD1 is strongly upregulated in CAFs and under direct negative control of AR, and its loss impairs the pro-tumorigenic potential of CAFs. ANKRD1 controls a CAF-specific gene expression program and is associated with poorer survival of HNSCC, lung, and cervical SCC patients. Mechanistically, ANKRD1 binds to the chromatin on CAF gene regulatory regions in a complex with the AP1 transcription factor family. We show that ANKRD1 enhances the AP1 DNA binding activity to CAF gene promoters. Targeting ANKRD1 with the FANA antisense oligonucleotides reverts CAFs into a normal fibroblast, disrupts AP1 complex formation, and blocks CAF’s pro-tumorigenic potential in an orthotopic model of SCC, thus representing an exciting target for stroma-oriented cancer therapy.
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| Overall design |
Human dermal fibrloblasts with ANKRD1 overexpression versus control were run in triplicates.
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| Contributor(s) |
Luigi M, Dotto GP |
| Citation(s) |
38310103 |
| Submission date |
Nov 17, 2022 |
| Last update date |
Feb 09, 2024 |
| Contact name |
Paola Ostano |
| Organization name |
Fondazione Edo ed Elvo Tempia
|
| Street address |
via Malta 3
|
| City |
Biella |
| ZIP/Postal code |
13900 |
| Country |
Italy |
| |
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| Platforms (1) |
| GPL23126 |
[Clariom_D_Human] Affymetrix Human Clariom D Assay [transcript (gene) version] |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA902731 |
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