Abstract
Copper chaperone for superoxide dismutase (CCS) is a critical component of oxidation–reduction system and functions as a potential tumor promoter in several cancers. However, the function and clinical significance of CCS in breast cancer remain unclear. Here, we found CCS was highly expressed in breast cancer, where it promoted breast cancer cell proliferation and migration. Suppression of CCS expression was sufficient to attenuate the phosphorylation level of ERK1/2 and increase the accumulation of reactive oxygen species (ROS). Mechanistically, we found that knockdown of CCS decreases the activity of ERK1/2 mediated by the accumulation of ROS, which leads to the inhibition of cell proliferation and migration. In summary, these results indicated that CCS promotes the growth and migration of breast cancer cells via regulating the ERK1/2 activity mediated by ROS.
Highlights
Breast cancer is the leading cause of cancer-related deaths in women worldwide (Christofori, 2006; Bray et al, 2018)
To determine the role of Copper chaperone for superoxide dismutase (CCS) in human breast cancer, we first examined the expression of CCS utilizing Gene Expression Omnibus (GEO) profiles; we found that the expression of CCS was higher in breast cancer tissue than in noncancerous tissue (Figure 1A, GSE9574)
Rapid cellular growth and migratory abilities play a crucial role in tumorigenesis and metastasis, which have been recognized to be associated with reactive oxygen species (ROS) levels (Aykin-Burns et al, 2009; Doskey et al, 2016)
Summary
Breast cancer is the leading cause of cancer-related deaths in women worldwide (Christofori, 2006; Bray et al, 2018). Breast cancer patients with metastases have an extremely poor prognosis (Gupta et al, 2005; Bacac and Stamenkovic, 2008; Thiery, 2009; Chaffer and Weinberg, 2011; Valastyan and Weinberg, 2011). A redox-active transition metal essential for most living organisms, serves as a catalytic cofactor for enzymes that function in antioxidant defense, iron homeostasis, cellular respiration, and a variety of biochemical processes (Mandinov et al, 2003; Lowndes and Harris, 2005; Ashino et al, 2010; Xu et al, 2016; Sciegienka et al, 2017). The uncontrolled accumulation of copper could lead to increased oxidative stress and inappropriate binding to macromolecules.
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