Journal article
IL-1β expression driven by androgen receptor absence or inactivation promotes prostate cancer bone metastasis
Cancer research communications, v 2(12), pp 1545-1557
01 Dec 2022
PMID: 36561929
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
We report the inverse association between the expression of androgen receptor (AR) and interleukin-1beta (IL-1β) in a cohort of patients with metastatic castration resistant prostate cancer (mCRPC). We also discovered that AR represses the IL-1β gene by binding an androgen response element (ARE) half-site located within the promoter, which explains the IL-1β expression in AR-negative (AR
NEG
) cancer cells. Consistently, androgen-depletion or AR-pathway inhibitors (ARIs) de-repressed IL-1β in AR
POS
cancer cells, both
in vitro
and
in vivo
. The AR transcriptional repression is sustained by histone de-acetylation at the H3K27 mark in the IL-1β promoter. Notably, patients’ data suggest that DNA methylation prevents IL-1β expression, even if the AR-signaling axis is inactive. Our previous studies show that secreted IL-1β supports metastatic progression in mice by altering the transcriptome of tumor-associated bone stroma. Thus, in prostate cancer patients harboring AR
NEG
tumor cells or treated with ADT/ARIs, and with the IL-1β gene unmethylated, IL-1β could condition the metastatic microenvironment to sustain disease progression.
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Details
- Title
- IL-1β expression driven by androgen receptor absence or inactivation promotes prostate cancer bone metastasis
- Creators
- Anthony DiNatale - Drexel UniversityAsurayya Worrede - AstraZeneca (United States), Gaithersburg, MD, United StatesWaleed Iqbal - Drexel UniversityMichael Marchioli - Drexel UniversityAllison Toth - Drexel UniversityMartin Sjöström - University of California, San FranciscoXiaolin Zhu - University of California, San FranciscoEva Corey - University of WashingtonFelix Y. Feng - University of California, San FranciscoWanding Zhou - University of PennsylvaniaAlessandro Fatatis - Drexel University
- Publication Details
- Cancer research communications, v 2(12), pp 1545-1557
- Publisher
- American Association for Cancer Research (AACR)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine; Pharmacology and Physiology; Drexel University
- Web of Science ID
- WOS:001033739500001
- Scopus ID
- 2-s2.0-85192635759
- Other Identifier
- 991020100191904721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- Web of Science research areas
- Oncology