Title |
Extracellular matrix protein 1 regulates cell proliferation and trastuzumab resistance through activation of epidermal growth factor signaling
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Published in |
Breast Cancer Research, December 2014
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DOI | 10.1186/s13058-014-0479-6 |
Pubmed ID | |
Authors |
Kyung-min Lee, Keesoo Nam, Sunhwa Oh, Juyeon Lim, Young-Pil Kim, Jong Won Lee, Jong-Han Yu, Sei-Hyun Ahn, Sung-Bae Kim, Dong-Young Noh, Taehoon Lee, Incheol Shin |
Abstract |
IntroductionExtracellular 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 cellular signaling in breast cancer, and potential mechanisms for its effects.MethodsIn 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 cellular signalings in vitro and in vivo. Moreover, tissues and sera of patients with breast cancer were used to confirm the effect of ECM1.ResultsECM1 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 up-regulation 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.ConclusionsECM1 has important roles in both cancer development and trastuzumab resistance in breast cancer through activation of EGFR signaling. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 31 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 8 | 26% |
Student > Doctoral Student | 4 | 13% |
Other | 4 | 13% |
Student > Master | 2 | 6% |
Student > Ph. D. Student | 2 | 6% |
Other | 3 | 10% |
Unknown | 8 | 26% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 8 | 26% |
Medicine and Dentistry | 5 | 16% |
Immunology and Microbiology | 2 | 6% |
Agricultural and Biological Sciences | 1 | 3% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 3% |
Other | 4 | 13% |
Unknown | 10 | 32% |