Aberrant expression of histone deacetylase 6 in oral squamous cell carcinoma

Abstract

Abstract.The structure and function of chromatin can be altered by modifications to histone. Histone acetylation is a reversible process governed by histone acetyltransferases and histone deacetylases (HDACs). HDAC6 is a subtype of the HDAC family that deacetylates ·-tubulin and increases cell motility. We investigated the expression levels of HDAC6 mRNA and protein expression in oral squamous cell carcinoma (OSCC)-derived cell lines and human primary OSCCs to elucidate the potential involvement of HDAC6 in OSCC. Using quantitative real-time reverse transcription polymerase chain reaction and Western blots on nine OSCC-derived cell lines and normal oral keratinocytes (NOKs), HDAC6 mRNA and protein expression were commonly up-regulated in all cell lines compared with the NOKs. Immunofluorescence analysis detected HDAC6 protein in the cytoplasm of OSCC cell lines. Similar to OSCC cell lines, high frequencies of HDAC6 up-regulation were evident in both mRNA (74%) and protein (51%) levels of primary tumors. Among the clinical variables analyzed, the clinical tumor stage was found to be associated with the HDAC6 expression states. The analysis indicated a significant difference in the HDAC6 expression level between the early stage (stage I and II) and advancedstage (stage III and IV) tumors (P=0.014). These results suggest that HDAC6 expression may be correlated with tumor aggressiveness and offer clues to the planning of new treatments.

Inhibition of HDAC6 Protein Enhances Bortezomib-induced Apoptosis in Head and Neck Squamous Cell Carcinoma (HNSCC) by Reducing Autophagy

“…Moreover, it will be interesting to examine how HDAC6 interacts with mTOR signaling. HDAC6 has been found to be highly expressed in HNSCC tissues (31). Based on our results, it is possible that HDAC6 might be a critical regulator of the cell protective response mediating the molecular network between ER stress, autophagy, and apoptosis to develop resistance to chemotherapy in HNSCC.…”

“…HDAC6 has also been shown to deacetylate heat shock protein 90 (HSP90) and to modulate its chaperone activity to restore ER homeostasis (30). Moreover, the aberrant expression of HDAC6 has been reported in HNSCC patient tissues (31). Based on these findings, we hypothesized that HDAC6 might be a critical regulator of the cell protective response mediating the molecular network between ER stress, autophagy, and apoptosis to develop resistance to chemotherapy in HNSCC.…”

HDAC6, at the crossroads between cytoskeleton and cell signaling by acetylation and ubiquitination

“…HDAC6 expression and functions may also be linked to cell transformation. Depending on the type of cancer, the HDAC6 expression level could be considered either as a good prognosis indicator (Zhang et al, 2004) or, in contrast, as a predictor of poor prognosis and tumor aggressiveness (Osada et al, 2004;Hayashi and Yamaguchi, 2006;Sakuma et al, 2006). Indeed, HDAC6 detection has been reported to correlate with survival in a subset of tamoxifen-treated ER-positive breast cancer patients (Saji et al, 2005).…”

ArabidopsisPaired Amphipathic Helix Proteins SNL1 and SNL2 Redundantly Regulate Primary Seed Dormancy via Abscisic Acid–Ethylene Antagonism Mediated by Histone Deacetylation

“…SIN3 has an important role in the regulation of centromeres, the cell cycle, and chromatin remodeling in several organisms (Kawaguchi et al, 2003;Sakuma et al, 2006;Wilson et al, 2006). Drosophila melanogaster sin3 null mutants die during the larval stage of development due to a delay in the G2 phase of the cell cycle (Pennetta and Pauli, 1998).…”