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Duong, Thu, Araujo Rincon, Mariana, Myneni, Nishanth, Burleson, Marieke. (1402). Genetic alterations in MED12 promote castration-resistant prostate cancer through modulation of GLI3 signaling. , 12(2), 63-70. doi: 10.22099/mbrc.2023.47346.1828
Thu Minh Duong; Mariana Araujo Rincon; Nishanth Myneni; Marieke Burleson. "Genetic alterations in MED12 promote castration-resistant prostate cancer through modulation of GLI3 signaling". , 12, 2, 1402, 63-70. doi: 10.22099/mbrc.2023.47346.1828
Duong, Thu, Araujo Rincon, Mariana, Myneni, Nishanth, Burleson, Marieke. (1402). 'Genetic alterations in MED12 promote castration-resistant prostate cancer through modulation of GLI3 signaling', , 12(2), pp. 63-70. doi: 10.22099/mbrc.2023.47346.1828
Duong, Thu, Araujo Rincon, Mariana, Myneni, Nishanth, Burleson, Marieke. Genetic alterations in MED12 promote castration-resistant prostate cancer through modulation of GLI3 signaling. , 1402; 12(2): 63-70. doi: 10.22099/mbrc.2023.47346.1828

Genetic alterations in MED12 promote castration-resistant prostate cancer through modulation of GLI3 signaling

Molecular Biology Research Communications
دوره 12، شماره 2، 2023، صفحه 63-70    اصل مقاله (404.38 K)
نوع مقاله: Original article
شناسه دیجیتال (DOI): 10.22099/mbrc.2023.47346.1828
نویسندگان
Thu Minh Duong1؛ Mariana Araujo Rincon2؛ Nishanth Myneni2؛ Marieke Burleson* 2
1Department of Molecular Medicine, UT Health San Antonio, San Antonio, TX, USA
2Department of Biology, University of the Incarnate Word, San Antonio, TX, USA
چکیده
Prostate cancer is a disease that depends on androgenic stimulation and is thus commonly treated with androgen deprivation therapy (ADT). ADT is highly successful initially; however, patients inevitably relapse at which point the cancer grows independently of androgens and is termed castration-resistant prostate cancer (CRPC). CRPC develops through various mechanisms, one of these being crosstalk of the androgen receptor (AR) signaling pathway with other signaling pathways. Congruently, prior work has shown that androgen deprivation induces SHH signaling, which subsequently promotes activation of AR-dependent gene expression to promote cell growth. Mechanistically, this crosstalk involves a physical interaction between AR and components of SHH signaling, specifically proteins of the GLI transcription factor family. These findings thus suggest that activation of SHH signaling could promote the recurrence of cell growth in the absence of androgens to ultimately lead to progression towards CRPC. In this study, we have investigated this mechanism in a subset of prostate cancer that harbors genetic alterations within the Mediator subunit 12 (MED12). We found that loss of MED12 promotes the expression of GLI3 target genes which subsequently drives excessive cell growth in the absence of androgens. Thus, we conclude that genetic alterations within MED12 promote CRPC through hyperactivated GLI3 dependent sonic hedgehog signaling.
کلیدواژه‌ها
MED12؛ castration-resistant prostate cancer؛ SHH signaling؛ GLI3؛ tumorigenesis
مراجع
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