Research Papers:

Regulation of FBXO4-mediated ICAM-1 protein stability in metastatic breast cancer

Jae-Hyeok Kang, Mi-Young Choi, Yan-Hong Cui, Neha Kaushik, Nizam Uddin, Ki-Chun Yoo, Min-Jung Kim and Su-Jae Lee _

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Oncotarget. 2017; 8:83100-83113. https://doi.org/10.18632/oncotarget.20912

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Jae-Hyeok Kang1,*, Mi-Young Choi1,*, Yan-Hong Cui1, Neha Kaushik1, Nizam Uddin2, Ki-Chun Yoo1, Min-Jung Kim3 and Su-Jae Lee1

1Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul, Korea

2Centre of Excellence in Molecular Biology (CEMB), University of The Panjab, Lahore, Pakistan

3Laboratory of Radiation Exposure and Therapeutics, National Radiation Emergency Medical Center, Korea Institute of Radiological and Medical Sciences, Seoul, Korea

*These authors have contributed equally to this work

Correspondence to:

Su-Jae Lee, email: [email protected]

Keywords: intercellular adhesion molecule-1, E3 ligase, FBXO4, stability, metastatic breast cancer

Received: July 21, 2017    Accepted: August 27, 2017    Published: September 15, 2017


Advanced or progressive cancers share common traits such as altered transcriptional modulation, genetic modification, and abnormal post-translational regulation. These processes influence protein stability and cellular activity. Intercellular adhesion molecule-1 (ICAM-1) is involved in the malignant progression of various human cancers, including breast, liver, renal, and pancreatic cancers, but protein stability has not been deal with in metastatic breast cancer. Additionally, the relevance of the stability maintenance of ICAM-1 protein remains obscure. Here, we identified a novel interaction of E3 ligase FBXO4 that is specifically presented to ICAM-1. To understand how FBXO4 modulates ICAM-1 stability, we investigated ICAM-1-overexpressing or knockdown metastatic/non-metastatic breast cancers. ICAM-1 was found to influence tumor progression and metastasis, whereas FBXO4 regulated aggressive tumorigenic conditions. These results demonstrate that FBXO4 is a major regulator of ICAM-1 stability and that alterations in the stability of ICAM-1 can influence therapeutic outcome in metastatic cancer.

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