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| Status |
Public on Apr 05, 2024 |
| Title |
Overcoming Lineage Plasticity and AR-Targeted Therapy Resistance in ZNF397-Deficient Prostate Cancer via TET2 Inhibition [RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Cancer cells exhibit phenotypical plasticity and epigenetic reprogramming, which allows them to evade lineage-dependent targeted treatments by adopting lineage plasticity. The underlying mechanisms by which cancer cells exploit the epigenetic regulatory machinery to acquire lineage plasticity and therapy resistance remain poorly understood. We identified Zinc Finger Protein 397 (ZNF397) as a bona fide coactivator of the androgen receptor (AR), essential for the transcriptional program governing AR-driven luminal lineage. ZNF397 deficiency facilitates the transition of cancer cell from an AR-driven luminal lineage to a Ten-Eleven Translocation 2 (TET2)-driven lineage plastic state, ultimately promoting resistance to therapies inhibiting AR signaling. Intriguingly, our findings indicate that a TET2 inhibitor can eliminate the AR targeted therapies resistance in ZNF397-deficient tumors. These insights uncover a novel mechanism through which prostate cancer acquires lineage plasticity via epigenetic rewiring and offers promising implications for clinical interventions designed to overcome therapy resistance dictated by lineage plasticity.
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| Overall design |
Examination of transcriptomic changes in LNCaP/AR prostate cancer cell lines with modifications of ZNF397 gene. There is total 4 different conditions with 3 biological replicates each.
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| Contributor(s) |
Mu P |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Apr 25, 2023 |
| Last update date |
Apr 05, 2024 |
| Contact name |
Ping Mu |
| E-mail(s) |
muping817@gmail.com
|
| Organization name |
University of Texas Southwestern Medical Cente
|
| Street address |
5323 Harry Hines Blvd.
|
| City |
Dallas |
| State/province |
Texas |
| ZIP/Postal code |
75390 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE230602 |
Overcoming Lineage Plasticity and AR-Targeted Therapy Resistance in ZNF397-Deficient Prostate Cancer via TET2 Inhibition |
|
| Relations |
| BioProject |
PRJNA961832 |
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