Overexpression of HPV16 E6* Alters β-Integrin and Mitochondrial Dysfunction Pathways in Cervical Cancer Cells

Cancer Genomics - Proteomics

MARIA FILIPPOVA²  VALERY FILIPPOV²  WHITNEY EVANS²  PENELOPE DUERKSEN-HUGHES²  GUANGYU ZHANG²  SVETLANA BASHKIROVA²  MARK E. REEVES¹ 

[1] epartment of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA, U.S.A.enter for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine, Loma Linda, CA, U.S.A.epartment of Surgery, Loma Linda University School of Medicine, and Surgical Oncology Research Laboratory, Loma Linda VA Medical Center, Loma Linda, CA, U.S.A.epartment of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA, U.S.A.epartment of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA, U.S.A.enter for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine, Loma Linda, CA, U.S.A.epartment of Surgery, Loma Linda University School of Medicine, and Surgical Oncology Research Laboratory, Loma Linda VA Medical Center, Loma Linda, CA, U.S.A.enter for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine, Loma Linda, CA, U.S.A.epartment of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA, U.S.A.enter for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine, Loma Linda, CA, U.S.A.epartment of Surgery, Loma Linda University School of Medicine, and Surgical Oncology Research Laboratory, Loma Linda VA Medical Center, Loma Linda, CA, U.S.A.epartment of Surgery, Loma Linda University School of Medicine, and Surgical Oncology Research Laboratory, Loma Linda VA Medical Center, Loma Linda, CA, U.S.A.epartment of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA, U.S.A.enter for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine, Loma Linda, CA, U.S.A.epartment of Surgery, Loma Linda University School of Medicine, and Surgical Oncology Research Laboratory, Loma Linda VA Medical Center, Loma Linda, CA, U.S.A.;epartment of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA, U.S.A.enter for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine, Loma Linda, CA, U.S.A.epartment of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA, U.S.A.epartment of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA, U.S.A.enter for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine, Loma Linda, CA, U.S.A.enter for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine, Loma Linda, CA, U.S.A.epartment of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA, U.S.A.enter for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine, Loma Linda, CA, U.S.A.

关键词: Human papillomavirus;    E6*;    alternative splicing;    oxidative stress;    RhoA GTPase;    kindlin-1;    alkaline phosphatase;    cell spreading;    DNA damage;    mitochondrial membrane potential;    oxidative phosphorylation;    β-integrin;    glutathione;    mitochondrial membrane depolarization;    electron transport chain;    Ingenuity Pathway Analysis;   

DOI  :  

来源: Delinasios GJ CO

【 摘 要 】

Background: High-risk human papillomaviruses (HPV) cause nearly all cases of cervical cancer, as well as many types of oral and anogenital cancer. Alternative splicing increases the capacity of the HPV genome to encode the proteins necessary for successful completion of its infectious life cycle. However, the roles of these splice variants, including E6*, the smaller splice isoform of the E6 oncogene, in carcinogenesis are not clear. Materials and Methods: SiHa (HPV16+) and C33A (HPV−) cells were transfected with the E6* plasmid, and tandem mass tag-labeled protein levels were quantified by mass spectrometry. Proteomic analyses identified pathways affected by E6* in both HPV+ and HPV− cells, and pathways were validated using in vitro methods. Results: A total of 4,300 proteins were identified and quantified in lysates of SiHa and C33A cells with and without HPV16 E6* expression. SiHa and C33A cells expressing E6* underwent changes in protein expression affecting integrin signaling and mitochondrial dysfunction pathways, respectively. Subsequent experiments were performed to validate selected E6*-mediated alterations in protein levels. Conclusion: E6* modifies the expression of proteins involved in mitochondrial dysfunction and oxidative phosphorylation in C33A cells, and β-integrin signaling in SiHa cells.

【 授权许可】

Unknown