The Deubiquitinase USP28 Stabilizes LSD1 and Confers Stem-Cell-like Traits to Breast Cancer Cells

Yadi Wu; Yifan Wang; Xiuwei H. Yang; Tiebang Kang; Yongxiang Zhao; Chi Wang; B. Mark Evers; Binhua P. Zhou

doi:10.1016/j.celrep.2013.08.030

The Deubiquitinase USP28 Stabilizes LSD1 and Confers Stem-Cell-like Traits to Breast Cancer Cells

Yadi Wu
, Yifan Wang
, Xiuwei H. Yang
, Tiebang Kang
, Yongxiang Zhao
, Chi Wang
, B. Mark Evers
, Binhua P. Zhou

Producción científica: Article › revisión exhaustiva

154 Citas (Scopus)

Resumen

LSD1 is a critical chromatin modulator that controls cellular pluripotency and differentiation through the demethylation of H3K4me1/2. Overexpression of LSD1 has been observed in many types of tumors and is correlated with its oncogenic effects in tumorigenesis. However, the mechanism leading to LSD1 upregulation in tumors remains unclear. Using an unbiased siRNA screening against all the human deubiquitinases, we identified USP28 as a bona fide deubiquitinase of LSD1. USP28 interacted with and stabilized LSD1 via deubiquitination. USP28 overexpression correlated with LSD1 upregulation in multiple cancer cell lines and breast tumor samples. Knockdown of USP28 resulted in LSD1 destabilization, leading to the suppression of cancer stem cell (CSC)-like characteristics invitro and inhibition of tumorigenicity invivo, which can be rescued by ectopic LSD1 expression. Our study reveals a critical mechanism underlying the epigenetic regulation by USP28 and provides another treatment approach against breast cancer

Idioma original	English
Páginas (desde-hasta)	224-236
Número de páginas	13
Publicación	Cell Reports
Volumen	5
N.º	1
DOI	https://doi.org/10.1016/j.celrep.2013.08.030
Estado	Published - oct 17 2013

Nota bibliográfica

Funding Information:
We thank Cathy Anthony for critical reading and editing of this manuscript. This work was supported by grants from NIH (2 RO1CA125454), Susan G. Komen Foundation (KG081310), Mary Kay Ash Foundation (to B.P.Z.), and American Cancer Society Research Scholar Award (RSG13187-01 to Y.W.).

Financiación

We thank Cathy Anthony for critical reading and editing of this manuscript. This work was supported by grants from NIH (2 RO1CA125454), Susan G. Komen Foundation (KG081310), Mary Kay Ash Foundation (to B.P.Z.), and American Cancer Society Research Scholar Award (RSG13187-01 to Y.W.).

Financiadores	Número del financiador
National Institutes of Health (NIH)
American Cancer Society-Michigan Cancer Research Fund	RSG13187-01
National Childhood Cancer Registry – National Cancer Institute	R01CA125454
Mary Kay Ash Foundation
Susan G Komen Foundation	KG081310

ODS de las Naciones Unidas

Este resultado contribuye a los siguientes Objetivos de Desarrollo Sostenible

Good health and well being

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.celrep.2013.08.030

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title = "The Deubiquitinase USP28 Stabilizes LSD1 and Confers Stem-Cell-like Traits to Breast Cancer Cells",

abstract = "LSD1 is a critical chromatin modulator that controls cellular pluripotency and differentiation through the demethylation of H3K4me1/2. Overexpression of LSD1 has been observed in many types of tumors and is correlated with its oncogenic effects in tumorigenesis. However, the mechanism leading to LSD1 upregulation in tumors remains unclear. Using an unbiased siRNA screening against all the human deubiquitinases, we identified USP28 as a bona fide deubiquitinase of LSD1. USP28 interacted with and stabilized LSD1 via deubiquitination. USP28 overexpression correlated with LSD1 upregulation in multiple cancer cell lines and breast tumor samples. Knockdown of USP28 resulted in LSD1 destabilization, leading to the suppression of cancer stem cell (CSC)-like characteristics invitro and inhibition of tumorigenicity invivo, which can be rescued by ectopic LSD1 expression. Our study reveals a critical mechanism underlying the epigenetic regulation by USP28 and provides another treatment approach against breast cancer",

author = "Yadi Wu and Yifan Wang and Yang, \{Xiuwei H.\} and Tiebang Kang and Yongxiang Zhao and Chi Wang and Evers, \{B. Mark\} and Zhou, \{Binhua P.\}",

note = "Funding Information: We thank Cathy Anthony for critical reading and editing of this manuscript. This work was supported by grants from NIH (2 RO1CA125454), Susan G. Komen Foundation (KG081310), Mary Kay Ash Foundation (to B.P.Z.), and American Cancer Society Research Scholar Award (RSG13187-01 to Y.W.). ",

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AU - Wang, Chi

AU - Evers, B. Mark

AU - Zhou, Binhua P.

N1 - Funding Information: We thank Cathy Anthony for critical reading and editing of this manuscript. This work was supported by grants from NIH (2 RO1CA125454), Susan G. Komen Foundation (KG081310), Mary Kay Ash Foundation (to B.P.Z.), and American Cancer Society Research Scholar Award (RSG13187-01 to Y.W.).

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N2 - LSD1 is a critical chromatin modulator that controls cellular pluripotency and differentiation through the demethylation of H3K4me1/2. Overexpression of LSD1 has been observed in many types of tumors and is correlated with its oncogenic effects in tumorigenesis. However, the mechanism leading to LSD1 upregulation in tumors remains unclear. Using an unbiased siRNA screening against all the human deubiquitinases, we identified USP28 as a bona fide deubiquitinase of LSD1. USP28 interacted with and stabilized LSD1 via deubiquitination. USP28 overexpression correlated with LSD1 upregulation in multiple cancer cell lines and breast tumor samples. Knockdown of USP28 resulted in LSD1 destabilization, leading to the suppression of cancer stem cell (CSC)-like characteristics invitro and inhibition of tumorigenicity invivo, which can be rescued by ectopic LSD1 expression. Our study reveals a critical mechanism underlying the epigenetic regulation by USP28 and provides another treatment approach against breast cancer

AB - LSD1 is a critical chromatin modulator that controls cellular pluripotency and differentiation through the demethylation of H3K4me1/2. Overexpression of LSD1 has been observed in many types of tumors and is correlated with its oncogenic effects in tumorigenesis. However, the mechanism leading to LSD1 upregulation in tumors remains unclear. Using an unbiased siRNA screening against all the human deubiquitinases, we identified USP28 as a bona fide deubiquitinase of LSD1. USP28 interacted with and stabilized LSD1 via deubiquitination. USP28 overexpression correlated with LSD1 upregulation in multiple cancer cell lines and breast tumor samples. Knockdown of USP28 resulted in LSD1 destabilization, leading to the suppression of cancer stem cell (CSC)-like characteristics invitro and inhibition of tumorigenicity invivo, which can be rescued by ectopic LSD1 expression. Our study reveals a critical mechanism underlying the epigenetic regulation by USP28 and provides another treatment approach against breast cancer

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The Deubiquitinase USP28 Stabilizes LSD1 and Confers Stem-Cell-like Traits to Breast Cancer Cells

Resumen

Nota bibliográfica

Financiación

ODS de las Naciones Unidas

ASJC Scopus subject areas

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