Quantitative phosphoproteomics reveals genistein as a modulator of cell cycle and DNA damage response pathways in triple-negative breast cancer cells

International Journal of Oncology
Yi FangJing Wang

Abstract

Around one sixth of breast cancer cases are classified as triple-negative breast cancer (TNBC), named after the absence of the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2); however, patients with TNBC suffer from poor clinical outcome and shortage of targeted therapy. Genistein, an estrogenic soy isoflavone, shows anticancer effects in TNBC cells such as inducing G2/M cell cycle arrest and apoptosis. However, the underlying mechanism of its anticancer effects is poorly understood and its elucidation can help the development of novel therapeutic strategies for TNBC. In this study, by combining isobaric tag-based TMT labeling with titanium dioxide-based phosphopeptide enrichment, we quantitated 5,445 phosphorylation sites on 2,008 phosphoproteins in the TNBC cell line MDA-MB-231, upon genistein treatment. Our analysis revealed 332 genistein-regulated phosphorylation sites on 226 proteins. Our data show that genistein can regulate several biological processes during the cell cycle, including DNA replication, cohesin complex cleavage, and kinetochore formation. Furthermore, genistein can also activate DNA damage response, including activation of ATR and BRCA1 ...Continue Reading

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Citations

Sep 20, 2017·British Journal of Cancer·Sainan LiChuanyong Guo
Jun 8, 2018·Phytotherapy Research : PTR·Harini Anandhi SenthilkumarEdward J Kennelly
Jun 15, 2018·International Journal of Oncology·Aleksandra Nowak, Piotr Dziegiel
Dec 14, 2018·Clinical Science·Luis MolinaPamela Ehrenfeld
Apr 28, 2020·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Rama Rao MallaVenkata Ramesh Dasari
Aug 3, 2021·Oxidative Medicine and Cellular Longevity·Javad Sharifi-RadDaniela Calina

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Datasets Mentioned

BETA
MDA-MB-231
PXD002735

Methods Mentioned

BETA
ubiquitination

Software Mentioned

Andromeda
PANTHER
MaxQuant
DAVID functional
DAVID
PANTHER System

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