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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.
AuthorsEmine C Koc, Ebru Haciosmanoglu, Pier Paolo Claudio, Allison Wolf, Luigi Califano, Marco Friscia, Antonio Cortese, Hasan Koc
JournalMitochondrion (Mitochondrion) Vol. 24 Pg. 113-21 (Sep 2015) ISSN: 1872-8278 [Electronic] Netherlands
PMID26238294 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 Elsevier B.V. and Mitochondria Research Society. All rights reserved.
Chemical References
  • Mitochondrial Proteins
Topics
  • Aged
  • Blotting, Western
  • Carcinoma, Squamous Cell (pathology)
  • Female
  • Gene Expression Profiling
  • Head and Neck Neoplasms (pathology)
  • Humans
  • Male
  • Middle Aged
  • Mitochondria (enzymology, genetics, pathology)
  • Mitochondrial Proteins (biosynthesis)
  • Oxidative Phosphorylation
  • Protein Biosynthesis

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