Role of H-Ras/ERK signaling in carbon nanotube-induced neoplastic-like transformation of human mesothelial cells.
Lohcharoenkal-W; Wang-L; Stueckle-TA; Park-J; Tse-W; Dinu-C-Z; Rohanasakul-Y
Front Physiol 2014 Jun; 5:222
Rapid development and deployment of engineered nanomaterials such as carbon nanotubes (CNTs) in various commercial and biomedical applications have raised concerns about their potential adverse health effects, especially their long-term effects which have not been well addressed. We demonstrated here that prolonged exposure of human mesothelial cells to single-walled CNT (SWCNT) induced neoplastic-like transformation as indicated by anchorage-independent cell growth and increased cell invasiveness. Such transformation was associated with an up-regulation of H-Ras and activation of ERK1/2. Downregulation of H-Ras by siRNA or inactivation of ERK by chemical inhibitor effectrively inhibited the aggressive phenotype of SWCNT-exposed cells. Integrin alpha V and cortactin, but not epitheial-mesenchymal transition (EMT) transcriptional regulators, were up-regulated in the SWCNT-exposed cells, suggesting their role in the aggressive phenotype. Cortactin expression was shown to be controlled by the H-Ras/ERK signaling. Thus, our results indicate a novel role of H-Ras/ERK signaling and cortactin in the aggressive transformation of human mosethelial cells by SWCNT.
Nanotechnology; Carcinogens; Biomedical-engineering; Health-hazards; Exposure-levels; Risk-factors; Humans; Mesothelial-cells; Cell-function; Cellular-function; Neoplastic-transformation;
Author Keywords: mesothelial cells; H-Ras; SWCNT; ERK; cortactin; cell transformation
Yon Rojanasakul, Department of Pharmaceutical Sciences and Mary Babb Randolph Cancer Center, West Virginia University, 5706 Medical Center Dr., Morgantown, WV 26506
Frontiers in Physiology