Year: 2015
Type: article
Abstract: // Lingzhi Li 1 , Yongju Lu 1 , Paul M. Stemmer 1, 2 , Fei Chen 1 1 Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA 2 The Proteomics Core and Institute of Environmental Health Sciences, School of Medicine, Wayne State University, Detroit, MI 48201, USA Correspondence to: Fei Chen, e-mail: [email protected] Keywords: arsenic, Akt, filamin A, migration, patient survival Received: February 12, 2015 Accepted: March 14, 2015 Published: April 03, 2015 ABSTRACT We had previously reported that trivalent arsenic (As 3+ ), a well-known environmental carcinogen, induces phosphorylation of several putative Akt substrates. In the present report, we characterized one of these substrates by immunoprecipitation and proteomics analysis. The results indicate that a cytoskeleton remodeling protein, filamin A, with a molecular weight around 280 kDa, is phosphorylated by Akt in HEK-293 cells treated with As 3+ , which was also confirmed in human bronchial epithelial cell line, BEAS-2B cells. Additional biochemical and biological studies revealed that serine 2152 (S2152) of filamin A is phosphorylated by activated Akt in the cells treated with As 3+ . To further confirm the importance of Akt-dependent filamin A S2152 phosphorylation in As 3+ -induced cell migration, we over-expressed either wild type filamin A or the mutated filamin A in which the S2152 was substituted with alanine (S2152A). The capability of cell migration was reduced significantly in the cells expressing the mutated filamin A (S2152A). Clinically, we found that increased expression of filamin A predicts poorer overall survival of the lung cancer patients with adenocarcinoma. Thus, these data suggest that Akt dependent filamin A phosphorylation is one of the key events in mediating As 3+ -induced carcinogenesis. Antagonizing Akt signaling can ameliorate As 3+ -induced filamin A phosphorylation and cell migration, which may serve as a molecular targeting strategy for malignancies associated with environmental As 3+ exposure.
Source: Oncotarget
Authors: Lingzhi Li, Yongju Lu, Paul M. Stemmer, Fei Chen
Language: English
Subfield: Environmental Chemistry
Field: Environmental Science
Domain: Physical Sciences
Open Access status: diamond
Awards: G1233667601, Orbitrap Velos with ETD for Wayne State Proteomics, MicroRNA-190 and Oxidative Stress in Arsenic carcinogenesis, Center for Urban Responses to Environmental Stressors (CURES), G5967209050, Mdig gene and histone demethylation in lung cancer, G9000119117, CANCER CENTER SUPPORT GRANT
OpenAlex ID: W1856128729