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