FOXK2 transcription factor suppresses ERα-positive breast cancer cell growth through down-regulating the stability of ERα via mechanism involving BRCA1/BARD1.

Scientific Reports
Ying LiuHuijian Wu

Abstract

Estrogen receptors (ERs) are critical regulators of breast cancer development. Identification of molecules that regulate the function of ERs may facilitate the development of more effective breast cancer treatment strategies. In this study, we showed that the forkhead transcription factor FOXK2 interacted with ERα, and inhibited ERα-regulated transcriptional activities by enhancing the ubiquitin-mediated degradation of ERα. This process involved the interaction between FOXK2 and BRCA1/BARD1, the E3 ubiquitin ligase of ERα. FOXK2 interacted with BARD1 and acted as a scaffold protein for BRCA1/BARD1 and ERα, leading to enhanced degradation of ERα, which eventually accounted for its decreased transcriptional activity. Consistent with these observations, overexpression of FOXK2 inhibited the transcriptional activity of ERα, decreased the transcription of ERα target genes, and suppressed the proliferation of ERα-positive breast cancer cells. In contract, knockdown of FOXK2 in MCF-7 cells promoted cell proliferation. However, when ERα was also knocked down, knockdown of FOXK2 had no effect on cell proliferation. These findings suggested that FOXK2 might act as a negative regulator of ERα, and its association with both ERα and BRCA1/B...Continue Reading

References

Sep 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·C LiR B Gaynor
Aug 12, 1998·The Journal of Steroid Biochemistry and Molecular Biology·O W PrallR L Sutherland
Oct 6, 1998·Annual Review of Biochemistry·A Hershko, A Ciechanover
May 8, 2000·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·A CiechanoverA L Schwartz
Jan 16, 2002·Current Opinion in Genetics & Development·Richard Baer, Thomas Ludwig
Sep 26, 2002·Developmental Biology·Peter Carlsson, Margit Mahlapuu
Jan 28, 2003·Cancer·Judith Clancy Keen, Nancy E Davidson
Jun 23, 2004·Critical Reviews in Oncology/hematology·Nadine PlatetMarcel Garcia
May 19, 2005·Molecular and Cellular Biology·Mathilde CalligéHélène Richard-Foy
Oct 28, 2005·Essays in Biochemistry·Helen C Ardley, Philip A Robinson
Mar 30, 2007·Proceedings of the National Academy of Sciences of the United States of America·Catherine M EakinRachel E Klevit
Oct 19, 2007·Nature Reviews. Cancer·Stephen S Myatt, Eric W-F Lam
Mar 11, 2009·Nature Reviews. Genetics·Sridhar Hannenhalli, Klaus H Kaestner
Jan 26, 2010·Journal of Biochemistry·Yoshito Fujii, Michio Nakamura
Jul 9, 2010·The Journal of Biological Chemistry·Yu ZhangYongfeng Shang
Sep 3, 2010·The Journal of Biological Chemistry·Anett MaraisAndrew D Sharrocks
Mar 8, 2011·The Journal of Biological Chemistry·Yanyan LiYongfeng Shang
Apr 13, 2012·Journal of Cellular Physiology·Xinrong XingHuijian Wu
Oct 12, 2012·Breast Cancer Research and Treatment·M L PannoS Andò
May 3, 2013·Molecular Cancer Research : MCR·Kaiming Xu, Hui-Kuo G Shu
Oct 9, 2013·Biochemical and Biophysical Research Communications·Yu ZhangPeter C K Leung
Jan 16, 2014·Molecular Endocrinology·Thiziri Nait AchourStéphan Jalaguier
Feb 6, 2014·PloS One·Coralie PoulardMuriel Le Romancer
Apr 23, 2014·The Journal of Cell Biology·Lesley A KaneRichard J Youle
Apr 25, 2014·Proceedings of the National Academy of Sciences of the United States of America·Rahul S SamantPaul Workman
Jun 20, 2014·Molecular Biology of the Cell·Hailian BiHuijian Wu

❮ Previous
Next ❯

Citations

Feb 16, 2016·Cancer Cell International·Marco Allán Pérez-SolisArturo Aguilar-Rojas
Jan 8, 2016·The International Journal of Biochemistry & Cell Biology·Irmgard Irminger-FingerMaxim Pilyugin
Dec 23, 2016·Biochemical and Biophysical Research Communications·Yu QianZhenyu Feng
Jan 26, 2018·International Journal of Cancer. Journal International Du Cancer·Fan ZhangXu Zhang
Jun 23, 2020·Experimental and Therapeutic Medicine·Xiang AoYing Liu
Jun 17, 2020·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Xiang AoYing Liu
Mar 16, 2018·Oncogenesis·Gabriela Nestal de MoraesEric W-F Lam
Mar 23, 2019·Cancers·Gabriela Nestal de MoraesAndrew David Sharrocks
Dec 19, 2020·Open Medicine·Haotian LuYing Liu
Dec 15, 2020·Open Medicine·Jian KongWenbing Sun
May 28, 2019·Cancer Letters·Ying LiuJianxun Wang
Jun 20, 2021·Molecular Biology Reports·Xinjian QuWen Wen

❮ Previous
Next ❯

Methods Mentioned

BETA
ubiquitination
co-immunoprecipitation
immunoprecipitation
two-hybrid
pull-down
PCR
flow cytometry
two
transfection
two hybrid

Related Concepts

Related Feeds

Breast Cancer: BRCA1 & BRCA2

Mutations involving BRCA1, found on chromosome 17, and BRCA2, found on chromosome 13, increase the risk for specific cancers, such as breast cancer. Discover the last research on breast cancer BRCA1 and BRCA2 here.