ISG15 (interferon-stimulated gene 15), an ubiquitin-like protein (UBL), is a new tumor marker whose expression has been correlated with disease progression in bladder cancer and suggested to be prognostic for breast cancer. However, the molecular basis for, and the function of, ISG15 overexpression in tumors remain unclear. Here, we show that ISG15 overexpression in both breast cancer cells and oncogenic Ras-transformed mammary epithelial cells (MCF-10A) is due to elevated secretion of interferon-β. Moreover, interferon-β-ISG15 autocrine signaling in oncogenic Ras-transformed MCF-10A cells results in increased colony formation efficiency. Interestingly, gain of epithelial-mesenchymal transition (EMT) characteristics, including appearance of spindle-shaped cell morphology and EMT markers, as well as increased cell migration, in Ras-transformed MCF-10A cells is also dependent on interferon-β-ISG15 autocrine signaling. Our results demonstrate for the first time that tumor cell-secreted interferon-β may modulate tumor cell growth and migration through ISG15, suggesting potential cancer therapeutic approaches by antagonizing interferon autocrine signaling.
Date:
2011-04
Relation:
Cancer Research. 2011 Apr;71:Abstract number 3438.
