USP22 Positively Modulates ERα Action Via Its Deubiquitinase Activity in Breast Cancer

Overview

Journal Cell Death Differ

Specialty Cell Biology

Date 2020 Jun 5

PMID 32494025

Citations 20

Authors

Shengli Wang

Xinping Zhong

Chunyu Wang

Hao Luo

Lin Lin

Hongmiao Sun

Ge Sun

Kai Zeng

Renlong Zou

Wei Liu

Ning Sun

Huijuan Song

Wensu Liu

Qiang Zhang

Zhixuan Liao

Xiaochun Teng

Tingting Zhou

Xun Sun

Yue Zhao

Affiliations

Soon will be listed here.

Abstract

Estrogen receptor α (ERα) is the crucial factor in ERα-positive breast cancer progression. Endocrine therapies targeting ERα signaling is one of the widely used therapeutic strategies for breast cancer. However, a large number of the patients become refractory to therapy. Abnormal expression of ERα co-regulator facilitates breast cancer development and tendency of endocrine resistance. Thus, it is necessary to discover the novel co-regulators modulating ERα action. Here, we demonstrate that histone deubiquitinase USP22 is highly expressed in breast cancer samples compared with that in the benign tissue, and high expression of USP22 was significantly associated with poorer overall survival in BCa samples. Moreover, USP22 associates with ERα to be involved in maintenance of ERα stability. USP22 enhances ERα-induced transactivation. We further provide the evidence that USP22 is recruited together with ERα to cis-regulatory elements of ERα target gene. USP22 promotes cell growth even under hypoxia condition and with the treatment of ERα antagonist in breast cancer cells. Importantly, the deubiquitination activity of USP22 is required for its functions on maintenance of ERα stability, thereby enhancing ERα action and conferring endocrine resistance in breast cancer.

Citing Articles

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USP22 regulates APL differentiation via PML-RARα stabilization and IFN repression.

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USP22 supports the aggressive behavior of basal-like breast cancer by stimulating cellular respiration.

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MYSM1 acts as a novel co-activator of ERα to confer antiestrogen resistance in breast cancer.

Luan R, He M, Li H, Bai Y, Wang A, Sun G EMBO Mol Med. 2024; 16(1):10-39.

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References

Manavathi B, Dey O, Gajulapalli V, Bhatia R, Bugide S, Kumar R . Derailed estrogen signaling and breast cancer: an authentic couple. Endocr Rev. 2012; 34(1):1-32. PMC: 3565105. DOI: 10.1210/er.2011-1057. View

Ali S, Coombes R . Endocrine-responsive breast cancer and strategies for combating resistance. Nat Rev Cancer. 2003; 2(2):101-12. DOI: 10.1038/nrc721. View

Yang J, Altahan A, Jones D, Buffa F, Bridges E, Interiano R . Estrogen receptor-α directly regulates the hypoxia-inducible factor 1 pathway associated with antiestrogen response in breast cancer. Proc Natl Acad Sci U S A. 2015; 112(49):15172-7. PMC: 4679044. DOI: 10.1073/pnas.1422015112. View

Stender J, Nwachukwu J, Kastrati I, Kim Y, Strid T, Yakir M . Structural and Molecular Mechanisms of Cytokine-Mediated Endocrine Resistance in Human Breast Cancer Cells. Mol Cell. 2017; 65(6):1122-1135.e5. PMC: 5546241. DOI: 10.1016/j.molcel.2017.02.008. View

Bhatt S, Stender J, Joshi S, Wu G, Katzenellenbogen B . OCT-4: a novel estrogen receptor-α collaborator that promotes tamoxifen resistance in breast cancer cells. Oncogene. 2016; 35(44):5722-5734. DOI: 10.1038/onc.2016.105. View

De Marchi T, Foekens J, Umar A, Martens J . Endocrine therapy resistance in estrogen receptor (ER)-positive breast cancer. Drug Discov Today. 2016; 21(7):1181-8. DOI: 10.1016/j.drudis.2016.05.012. View

Le Romancer M, Poulard C, Cohen P, Sentis S, Renoir J, Corbo L . Cracking the estrogen receptor's posttranslational code in breast tumors. Endocr Rev. 2011; 32(5):597-622. DOI: 10.1210/er.2010-0016. View

Fujita N, Jaye D, Kajita M, Geigerman C, Moreno C, Wade P . MTA3, a Mi-2/NuRD complex subunit, regulates an invasive growth pathway in breast cancer. Cell. 2003; 113(2):207-19. DOI: 10.1016/s0092-8674(03)00234-4. View

Zhou W, Slingerland J . Links between oestrogen receptor activation and proteolysis: relevance to hormone-regulated cancer therapy. Nat Rev Cancer. 2014; 14(1):26-38. DOI: 10.1038/nrc3622. View

10.

Jin K, Park S, Teo W, Korangath P, Cho S, Yoshida T . HOXB7 Is an ERα Cofactor in the Activation of HER2 and Multiple ER Target Genes Leading to Endocrine Resistance. Cancer Discov. 2015; 5(9):944-59. PMC: 4560624. DOI: 10.1158/2159-8290.CD-15-0090. View

11.

Hurtado A, Holmes K, Ross-Innes C, Schmidt D, Carroll J . FOXA1 is a key determinant of estrogen receptor function and endocrine response. Nat Genet. 2010; 43(1):27-33. PMC: 3024537. DOI: 10.1038/ng.730. View

12.

Wade M, Jones D, Wilson L, Stockley J, Coffey K, Robson C . The histone demethylase enzyme KDM3A is a key estrogen receptor regulator in breast cancer. Nucleic Acids Res. 2014; 43(1):196-207. PMC: 4288188. DOI: 10.1093/nar/gku1298. View

13.

Gao W, Xiao R, Zhang W, Hu Y, Peng B, Li W . JMJD6 Licenses ERα-Dependent Enhancer and Coding Gene Activation by Modulating the Recruitment of the CARM1/MED12 Co-activator Complex. Mol Cell. 2018; 70(2):340-357.e8. PMC: 6258263. DOI: 10.1016/j.molcel.2018.03.006. View

14.

Zhao Y, Lang G, Ito S, Bonnet J, Metzger E, Sawatsubashi S . A TFTC/STAGA module mediates histone H2A and H2B deubiquitination, coactivates nuclear receptors, and counteracts heterochromatin silencing. Mol Cell. 2008; 29(1):92-101. DOI: 10.1016/j.molcel.2007.12.011. View

15.

Atanassov B, Evrard Y, Multani A, Zhang Z, Tora L, Devys D . Gcn5 and SAGA regulate shelterin protein turnover and telomere maintenance. Mol Cell. 2009; 35(3):352-64. PMC: 2749492. DOI: 10.1016/j.molcel.2009.06.015. View

16.

Lin Z, Yang H, Kong Q, Li J, Lee S, Gao B . USP22 antagonizes p53 transcriptional activation by deubiquitinating Sirt1 to suppress cell apoptosis and is required for mouse embryonic development. Mol Cell. 2012; 46(4):484-94. DOI: 10.1016/j.molcel.2012.03.024. View

17.

Atanassov B, Dent S . USP22 regulates cell proliferation by deubiquitinating the transcriptional regulator FBP1. EMBO Rep. 2011; 12(9):924-30. PMC: 3166460. DOI: 10.1038/embor.2011.140. View

18.

Gennaro V, Stanek T, Peck A, Sun Y, Wang F, Qie S . Control of CCND1 ubiquitylation by the catalytic SAGA subunit USP22 is essential for cell cycle progression through G1 in cancer cells. Proc Natl Acad Sci U S A. 2018; 115(40):E9298-E9307. PMC: 6176615. DOI: 10.1073/pnas.1807704115. View

19.

Glinsky G, Berezovska O, Glinskii A . Microarray analysis identifies a death-from-cancer signature predicting therapy failure in patients with multiple types of cancer. J Clin Invest. 2005; 115(6):1503-21. PMC: 1136989. DOI: 10.1172/JCI23412. View

20.

Glinsky G . Genomic models of metastatic cancer: functional analysis of death-from-cancer signature genes reveals aneuploid, anoikis-resistant, metastasis-enabling phenotype with altered cell cycle control and activated Polycomb Group (PcG) protein chromatin.... Cell Cycle. 2006; 5(11):1208-16. DOI: 10.4161/cc.5.11.2796. View