Forkhead box K2 modulates epirubicin and paclitaxel sensitivity through FOXO3a in breast cancer

Oncogenesis
G Nestal de MoraesE W-F Lam

Abstract

The forkhead transcription factor FOXK2 has recently been implicated in cancer cell proliferation and survival, but a role in cancer chemotherapeutic drug resistance has hitherto not been explored. Here we demonstrate that FOXK2 has a central role in mediating the cytotoxic drug response in breast cancer. Clonogenic and cell viability assays showed that enhanced FOXK2 expression sensitizes MCF-7 breast cancer cells to paclitaxel or epirubicin treatment, whereas FOXK2 depletion by small interfering RNAs (siRNAs) confers drug resistance. Our data also showed that the activation of the tumour suppressor FOXO3a by paclitaxel and epirubicin is mediated through the induction of FOXK2, as depletion of FOXK2 by siRNA limits the induction of FOXO3a by these drugs in MCF-7 cells. Chromatin immunoprecipitation (ChIP) analysis showed that in response to drug treatment, FOXK2 accumulates and binds to the proximal FOXO3a promoter region in MCF-7 cells. Furthermore, we also uncovered that FOXK2 is deregulated and, therefore, can express at high levels in the nucleus of both the paclitaxel and epirubicin drug-resistant MCF-7 cells. Our results showed that ectopically overexpressed FOXK2 accumulates in the nuclei of drug-resistant MCF-7 cells b...Continue Reading

References

Sep 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·C LiR B Gaynor
Oct 7, 2003·The Journal of Biological Chemistry·Andrew SuntersEric W-F Lam
Nov 15, 2006·Molecular and Cellular Biology·Yongjun TanRobert H Costa
Apr 9, 2008·Oncogene·K K HoE W-F Lam
Jul 23, 2008·Molecular Cancer Therapeutics·Jimmy M-M KwokEric W-F Lam
Mar 12, 2009·Molecular Cancer Therapeutics·Ursula B McGovernEric W-F Lam
Sep 3, 2010·The Journal of Biological Chemistry·Anett MaraisAndrew D Sharrocks
Mar 30, 2011·Current Drug Targets·Miranda S C WilsonEric W-F Lam
Oct 8, 2011·Biochimica Et Biophysica Acta·Chuay-Yeng KooEric W-F Lam
Nov 16, 2011·Molecular and Cellular Biology·Zongling JiAndrew D Sharrocks
Dec 1, 2011·The Journal of Biological Chemistry·Ka-Kei HoEric W-F Lam
Sep 15, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Nu ZhangSuyun Huang
Feb 8, 2013·Nature·Matthew R WarrEmmanuelle Passegué
Mar 22, 2013·Carcinogenesis·Mattaka KhongkowEric W-F Lam
Jun 26, 2013·Nature Reviews. Cancer·Eric W-F LamChuay-Yeng Koo
Sep 13, 2014·Journal of Cellular Physiology·Lars P van der HeideMarten P Smidt
Nov 18, 2014·Nature Cell Biology·Christopher John BowmanBrian David Dynlacht

❮ Previous
Next ❯

Citations

Jan 26, 2018·International Journal of Cancer. Journal International Du Cancer·Fan ZhangXu Zhang
May 7, 2020·Cancer Metastasis Reviews·Yannasittha Jiramongkol, Eric W-F Lam
Mar 16, 2018·Oncogenesis·Gabriela Nestal de MoraesEric W-F Lam
Mar 23, 2019·Cancers·Gabriela Nestal de MoraesAndrew David Sharrocks
Mar 27, 2019·Scientific Reports·Nehal GuptaSanjay K Srivastava
Dec 15, 2020·Open Medicine·Jian KongWenbing Sun
May 28, 2019·Cancer Letters·Ying LiuJianxun Wang

❮ Previous
Next ❯

Methods Mentioned

BETA
immunoprecipitation
nuclear translocation
PCR
ChIP
confocal microscopy
deubiquitination
transfections
transfection

Software Mentioned

SPSS

Related Concepts

Related Feeds

Breast Cancer: Chemo-Resistance

Some cancers are difficult to treat and aggressive including the "triple-negative" breast cancer. This type of cancer is chemoresistant even before chemotherapy begins. Here are the latest discoveries chemo-resistance in breast cancer.