title: Impaired mitochondrial protein synthesis in head and neck squamous cell carcinoma.
abstract: Human head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer type worldwide, possibly due to the significant role of alcohol and tobacco use in its development. Underlying most cancers are defects in mitochondrial functions such as energy metabolism and apoptosis. In fact, the mutations in mitochondrial DNA (mtDNA), which encode proteins for oxidative phosphorylation (OXPHOS), have been associated with human head and neck cancers. Here, we investigated the changes in the expression of OXPHOS complexes and the contribution of the defects in mitochondrial translation in the progression of HNSCC. Western blot analyses of the several stage IVA HNSCC primary tumors have shown reduction in the expression of COII and ATP5A of the OXPHOS complexes IV and V subunits, respectively. On the other hand, expression of the majority of the OXPHOS subunits, except complex II SDHB subunit, was impaired in a patient with a stage IV tumor with a regional lymph node. Interestingly, an overall reduction in one of the mitochondrial-encoded subunits of the complex IV, COII, accentuated a possible defect in mitochondrial translation machinery in two of the stage IVA tumors. Evidence provided in this study suggests for the first time that the mitochondrial translation defect(s) could be due to a decrease in the expression of one of the essential mitochondrial ribosomal proteins, MRPL11, in head and neck tumor biopsies. We also observed an acquired mitochondrial translation deficiency in the HN8 cell line derived from a lymph node metastasis but not in the HN22 cells derived from the primary tumor of the same patient. These seminal observations suggest that the mitochondrial translation machinery deserves further investigation for accurate molecular assessment and treatment of HNSCC.
authors.affiliation: Department of Biochemistry and Microbiology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, United States. Electronic address: koce@marshall.edu.
authors.forename: Emine C
authors.initials: EC
authors.lastname: Koc
authors.affiliation: Department of Biochemistry and Microbiology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, United States.
authors.forename: Ebru
authors.initials: E
authors.lastname: Haciosmanoglu
authors.affiliation: Department of Biochemistry and Microbiology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, United States; Department of Surgery, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, United States.
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Claudio
authors.affiliation: Department of Biochemistry and Microbiology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, United States.
authors.forename: Allison
authors.initials: A
authors.lastname: Wolf
authors.affiliation: Department of Maxillo-Facial Surgery, University of Naples "Federico II", Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Califano
authors.affiliation: Department of Maxillo-Facial Surgery, University of Naples "Federico II", Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Friscia
authors.affiliation: Department of Medicine and Surgery, Unit of Maxillofacial Surgery, University of Salerno, Salerno, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cortese
authors.affiliation: Department of Pharmaceutical Science and Research, School of Pharmacy, Marshall University, Huntington, WV 25755, United States.
authors.forename: Hasan
authors.initials: H
authors.lastname: Koc
mesh_terms: D000368:Aged; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D006258:Head and Neck Neoplasms / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D024101:Mitochondrial Proteins / Q000096:biosynthesis*; D010085:Oxidative Phosphorylation; D014176:Protein Biosynthesis
chemical_list: D024101:Mitochondrial Proteins
keywords: Head and neck cancer; MRPL11; Mitochondrial protein synthesis; Mitochondrial ribosomal proteins; Mitochondrial translation; Oxidative phosphorylation defect; Squamous cell carcinoma