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the c-myc–bmi1 axis is essential for setdb1-mediated breast tumourigenesis
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نویسنده
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xiao j.-f. ,sun q.-y. ,ding l.-w. ,chien w. ,liu x.-y. ,mayakonda a. ,jiang y.-y. ,loh x.-y. ,ran x.-b. ,doan n.b. ,castor b. ,chia d. ,said j.w. ,tan k.t. ,yang h. ,fu x.-y. ,lin d.-c. ,koeffler h.p.
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منبع
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journal of pathology - 2018 - دوره : 246 - شماره : 1 - صفحه:89 -102
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چکیده
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Characterising the activated oncogenic signalling that leads to advanced breast cancer is of clinical importance. here, we showed that set domain, bifurcated 1 (setdb1), a histone h3 lysine 9 methyltransferase, is aberrantly expressed and behaves as an oncogenic driver in breast cancer. setdb1 enhances c-myc and cyclin d1 expression by promoting the internal ribosome entry site (ires)-mediated translation of myc/ccnd1 mrna, resulting in prominent signalling of c-myc to promote cell cycle progression, and provides a growth/self-renewal advantage to breast cancer cells. the activated c-myc–bmi1 axis is essential for setdb1-mediated breast tumourigenesis, because silencing of either c-myc or bmi1 profoundly impairs the enhanced growth/colony formation conferred by setdb1. furthermore, c-myc directly binds to the setdb1 promoter region and enhances its transcription, suggesting a positive regulatory interplay between setdb1 and c-myc. in this study, we identified setdb1 as a prominent oncogene and characterised the underlying mechanism whereby setdb1 drives breast cancer, providing a therapeutic rationale for targeting setdb1–bmi1 signalling in breast cancer.
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کلیدواژه
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breast cancer ,c-myc–bmi1 axis ,setdb1
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آدرس
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national university of singapore, cancer science institute of singapore, singapore, national university of singapore, cancer science institute of singapore, singapore, national university of singapore, cancer science institute of singapore, singapore, ucla school of medicine, cedar-sinai medical center, division of hematology/oncology, united states, national university of singapore, cancer science institute of singapore, singapore, national university of singapore, cancer science institute of singapore, singapore, national university of singapore, cancer science institute of singapore, singapore, national university of singapore, cancer science institute of singapore, singapore, national university of singapore, cancer science institute of singapore, singapore, university of california, department of pathology, united states, university of california, department of pathology, united states, university of california, department of pathology, laboratory medicine, united states, university of california, department of pathology, united states, national university of singapore, cancer science institute of singapor, singapore, national university of singapore, cancer science institute of singapor, singapore, national university of singapore, yong loo lin school of medicine, cancer science institute of singapor, department of biochemistry, singapore, ucla school of medicine, cedar-sinai medical center, division of hematology/oncology, united states, national university of singapore, cancer science institute of singapore, division of hematology/oncology, united states. ucla school of medicine, cedar-sinai medical center, division of hematology/oncology, united states
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Authors
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