دورية أكاديمية
أعرض في EDS

Targeting hyaluronan-mediated motility receptor (HMMR) enhances response to androgen receptor signalling inhibitors in prostate cancer.

التفاصيل البيبلوغرافية
العنوان: Targeting hyaluronan-mediated motility receptor (HMMR) enhances response to androgen receptor signalling inhibitors in prostate cancer.
المؤلفون: Hinneh JA; South Australian Immunogenomics Cancer Institute, University of Adelaide, Adelaide, SA, 5000, Australia.; Freemason's Centre for Male Health and Wellbeing, University of Adelaide, Adelaide, SA, 5000, Australia.; Precision Cancer Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, SA, 5000, Australia.; Department of Urology, Nagoya University Graduate School of Medicine, Nagoya, Japan.; Adelaide Medical School, University of Adelaide, Adelaide, SA, 5005, Australia., Gillis JL; South Australian Immunogenomics Cancer Institute, University of Adelaide, Adelaide, SA, 5000, Australia.; Precision Cancer Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, SA, 5000, Australia.; Adelaide Medical School, University of Adelaide, Adelaide, SA, 5005, Australia., Mah CY; South Australian Immunogenomics Cancer Institute, University of Adelaide, Adelaide, SA, 5000, Australia.; Freemason's Centre for Male Health and Wellbeing, University of Adelaide, Adelaide, SA, 5000, Australia.; Precision Cancer Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, SA, 5000, Australia.; Adelaide Medical School, University of Adelaide, Adelaide, SA, 5005, Australia., Irani S; South Australian Immunogenomics Cancer Institute, University of Adelaide, Adelaide, SA, 5000, Australia.; Precision Cancer Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, SA, 5000, Australia.; Adelaide Medical School, University of Adelaide, Adelaide, SA, 5005, Australia., Shrestha RK; Freemason's Centre for Male Health and Wellbeing, University of Adelaide, Adelaide, SA, 5000, Australia.; Adelaide Medical School, University of Adelaide, Adelaide, SA, 5005, Australia.; College of Medicine and Public Health, Flinders University, Bedford Park, SA, 5042, Australia.; Flinders Health and Medical Research Institute, Flinders University, Bedford Park, SA, 5042, Australia., Ryan NK; South Australian Immunogenomics Cancer Institute, University of Adelaide, Adelaide, SA, 5000, Australia.; Precision Cancer Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, SA, 5000, Australia.; Adelaide Medical School, University of Adelaide, Adelaide, SA, 5005, Australia., Atsushi E; Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan., Nassar ZD; South Australian Immunogenomics Cancer Institute, University of Adelaide, Adelaide, SA, 5000, Australia.; Freemason's Centre for Male Health and Wellbeing, University of Adelaide, Adelaide, SA, 5000, Australia.; Precision Cancer Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, SA, 5000, Australia.; Adelaide Medical School, University of Adelaide, Adelaide, SA, 5005, Australia., Lynn DJ; Precision Cancer Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, SA, 5000, Australia.; College of Medicine and Public Health, Flinders University, Bedford Park, SA, 5042, Australia., Selth LA; Freemason's Centre for Male Health and Wellbeing, University of Adelaide, Adelaide, SA, 5000, Australia.; Adelaide Medical School, University of Adelaide, Adelaide, SA, 5005, Australia.; College of Medicine and Public Health, Flinders University, Bedford Park, SA, 5042, Australia.; Flinders Health and Medical Research Institute, Flinders University, Bedford Park, SA, 5042, Australia., Kato M; Department of Urology, Nagoya University Graduate School of Medicine, Nagoya, Japan., Centenera MM; South Australian Immunogenomics Cancer Institute, University of Adelaide, Adelaide, SA, 5000, Australia.; Freemason's Centre for Male Health and Wellbeing, University of Adelaide, Adelaide, SA, 5000, Australia.; Precision Cancer Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, SA, 5000, Australia.; Adelaide Medical School, University of Adelaide, Adelaide, SA, 5005, Australia., Butler LM; South Australian Immunogenomics Cancer Institute, University of Adelaide, Adelaide, SA, 5000, Australia. lisa.butler@adelaide.edu.au.; Freemason's Centre for Male Health and Wellbeing, University of Adelaide, Adelaide, SA, 5000, Australia. lisa.butler@adelaide.edu.au.; Precision Cancer Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, SA, 5000, Australia. lisa.butler@adelaide.edu.au.; Adelaide Medical School, University of Adelaide, Adelaide, SA, 5005, Australia. lisa.butler@adelaide.edu.au.
المصدر: British journal of cancer [Br J Cancer] 2023 Oct; Vol. 129 (8), pp. 1350-1361. Date of Electronic Publication: 2023 Sep 06.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group on behalf of Cancer Research UK Country of Publication: England NLM ID: 0370635 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-1827 (Electronic) Linking ISSN: 00070920 NLM ISO Abbreviation: Br J Cancer Subsets: MEDLINE
أسماء مطبوعة: Publication: 2002- : London : Nature Publishing Group on behalf of Cancer Research UK
Original Publication: London, Lewis.
مواضيع طبية MeSH: Prostatic Neoplasms*/drug therapy , Prostatic Neoplasms*/genetics , Prostatic Neoplasms*/metabolism , Prostatic Neoplasms, Castration-Resistant*/drug therapy, Male ; Humans ; Mice ; Animals ; Receptors, Androgen/genetics ; Receptors, Androgen/metabolism ; Cell Line, Tumor ; Nitriles/pharmacology ; RNA, Small Interfering/pharmacology ; Drug Resistance, Neoplasm/genetics ; Cell Proliferation
مستخلص: Background: Resistance to androgen receptor signalling inhibitors (ARSIs) represents a major clinical challenge in prostate cancer. We previously demonstrated that the ARSI enzalutamide inhibits only a subset of all AR-regulated genes, and hypothesise that the unaffected gene networks represent potential targets for therapeutic intervention. This study identified the hyaluronan-mediated motility receptor (HMMR) as a survival factor in prostate cancer and investigated its potential as a co-target for overcoming resistance to ARSIs.
Methods: RNA-seq, RT-qPCR and Western Blot were used to evaluate the regulation of HMMR by AR and ARSIs. HMMR inhibition was achieved via siRNA knockdown or pharmacological inhibition using 4-methylumbelliferone (4-MU) in prostate cancer cell lines, a mouse xenograft model and patient-derived explants (PDEs).
Results: HMMR was an AR-regulated factor that was unaffected by ARSIs. Genetic (siRNA) or pharmacological (4-MU) inhibition of HMMR significantly suppressed growth and induced apoptosis in hormone-sensitive and enzalutamide-resistant models of prostate cancer. Mechanistically, 4-MU inhibited AR nuclear translocation, AR protein expression and subsequent downstream AR signalling. 4-MU enhanced the growth-suppressive effects of 3 different ARSIs in vitro and, in combination with enzalutamide, restricted proliferation of prostate cancer cells in vivo and in PDEs.
Conclusion: Co-targeting HMMR and AR represents an effective strategy for improving response to ARSIs.
(© 2023. The Author(s).)
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المشرفين على المادة: 93T0T9GKNU (enzalutamide)
0 (Receptors, Androgen)
0 (hyaluronan-mediated motility receptor)
47341-71-9 (diethylstilbestrol monophosphate)
0 (Nitriles)
0 (RNA, Small Interfering)
تواريخ الأحداث: Date Created: 20230906 Date Completed: 20231023 Latest Revision: 20231103
رمز التحديث: 20231104
مُعرف محوري في PubMed: PMC10575850
DOI: 10.1038/s41416-023-02406-8
PMID: 37673961
قاعدة البيانات: MEDLINE
الوصف
تدمد:1532-1827
DOI:10.1038/s41416-023-02406-8