@article{6df15a41031b4c9089d77b29769cc24e,
title = "Epidermal growth factor receptor potentiates MCM7-mediated dna replication through tyrosine phosphorylation of lyn kinase in human cancers",
abstract = "Epidermal growth factor receptor (EGFR) initiates a signaling cascade that leads to DNA synthesis and cell proliferation, but its role in regulating DNA replication licensing is unclear. Here, we show that activated EGFR phosphorylates the p56 isoform of Lyn, p56Lyn, at Y32, which then phosphorylates MCM7, a licensing factor critical for DNA replication, at Y600 to increase its association with other minichromosome maintenance complex proteins, thereby promoting DNA synthesis complex assembly and cell proliferation. Both p56Lyn Y32 and MCM7 Y600 phosphorylation are enhanced in proliferating cells and correlated with poor survival of breast cancer patients. These results establish a signaling cascade in which EGFR enhances MCM7 phosphorylation and DNA replication through Lyn phosphorylation in human cancer cells.",
author = "Huang, {Tzu Hsuan} and Longfei Huo and Wang, {Ying Nai} and Weiya Xia and Yongkun Wei and Chang, {Shih Shin} and Chang, {Wei Chao} and Fang, {Yueh Fu} and Chen, {Chun Te} and Lang, {Jing Yu} and Chun Tu and Yan Wang and Hsu, {Ming Chuan} and Kuo, {Hsu Ping} and Ko, {How Wen} and Jia Shen and Lee, {Heng Huan} and Lee, {Pei Chih} and Yun Wu and Chen, {Chung Hsuan} and Hung, {Mien Chie}",
note = "Funding Information: We thank Dr. Yekaterina Khotskaya, Dr. Jennifer L. Hsu, and Dr. Stephanie A. Miller for editing this manuscript and the Center for Biological Pathways at MD Anderson Cancer Center for support. This study was funded in part by National Institutes of Health (CA109311, CA099031, and CCSG CA16672); Susan G. Komen Foundation (SAC100016); National Breast Cancer Foundation, Patel Memorial Breast Cancer Research Fund; The University of Texas MD Anderson-China Medical University and Hospital Sister Institution Fund (to M.-C.H.); Cancer Research Center of Excellence (DOH102-TD-C-111-005, Taiwan); Private University grant (NSC99-2632-B-039-001-MY3, Taiwan); Program for Stem Cell and Regenerative Medicine Frontier Research (NSC101-2321-B-039-001, Taiwan); International Research-Intensive Centers of Excellence in Taiwan (NSC102-2911-I-002-303, Taiwan); and National Science Council Taiwan Merit Postdoctoral Scholarship (TMS-94-2B-001 to Y.-N.W.). ",
year = "2013",
month = jun,
day = "10",
doi = "10.1016/j.ccr.2013.04.027",
language = "English (US)",
volume = "23",
pages = "796--810",
journal = "Cancer cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "6",
}