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Extracellular matrix protein 1 regulates cell proliferation and trastuzumab resistance through activation of epidermal growth factor signaling

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Authors
Lee, Kyung-min; Nam, Keesoo; Oh, Sunhwa; Lim, Juyeon; Kim, Young-Pil; Lee, Jong Won; Yu, Jong-Han; Ahn, Sei-Hyun; Kim, Sung-Bae; Noh, Dong-Young; Lee, Taehoon; Shin, Incheol
Issue Date
2014-12-11
Citation
Breast Cancer Research, 16(6):479
Abstract
Introduction
Extracellular matrix protein 1 (ECM1) is a secreted glycoprotein with putative functions in cell proliferation, angiogenesis and differentiation. Expression of ECM1 in several types of carcinoma suggests that it may promote tumor development. In this study, we investigated the role of ECM1 in oncogenic cell signaling in breast cancer, and potential mechanisms for its effects.

Methods
In order to find out the functional role of ECM1, we used the recombinant human ECM1 and viral transduction systems which stably regulated the expression level of ECM1. We examined the effect of ECM1 on cell proliferation and cell signaling in vitro and in vivo. Moreover, tissues and sera of patients with breast cancer were used to confirm the effect of ECM1.

Results
ECM1 protein was increased in trastuzumab-resistant (TR) cells, in association with trastuzumab resistance and cell proliferation. Through physical interaction with epidermal growth factor receptor (EGFR), ECM1 potentiated the phosphorylation of EGFR and extracellular signal-regulated kinase upon EGF treatment. Moreover, ECM1-induced galectin-3 cleavage through upregulation of matrix metalloproteinase 9 not only improved mucin 1 expression, but also increased EGFR and human epidermal growth factor receptor 3 protein stability as a secondary signaling.

Conclusions
ECM1 has important roles in both cancer development and trastuzumab resistance in breast cancer through activation of EGFR signaling.
ISSN
1465-542X
URI
http://hdl.handle.net/10371/117780
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College of Medicine/School of Medicine (의과대학/대학원)Program in Cancer Biology (협동과정-종양생물학전공)Journal Papers (저널논문_협동과정-종양생물학전공)
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