ABSTRACT
Epidermal growth factor receptor (EGFR) is highly expressed in head and neck squamous cell carcinoma (HNSCC) and correlates with poor prognosis. EGFR has been demonstrated to be associated with cancer stem cell traits in HNSCC. However, the underlying molecular mechanism is far from elucidated. Here, SOX2, one of the most important stem cell markers, was identified as a binding partner and substrate of EGFR. EGFR signaling inhibition decreases SOX2 expression by promoting its autophagic degradation. Mechanistically, EGFR activation induces SOX2 phosphorylation at the Y277 site and reduces its ubiquitination, which inhibits its association with p62 and subsequent autophagic degradation. Gefitinib, an EGFR tyrosine kinase inhibitor, shows in vitro and in vivo protective effects against oral cancer cells that can be reversed through autophagy inhibition. Our study suggests that EGFR plays an important role in the development of cancer stem cells by stabilizing SOX2. Targeting EGFR in combination with conventional chemotherapy might be a promising strategy for the treatment of HNSCC through elimination of cancer stem cells.
Subject(s)
Autophagy/physiology , Gefitinib/pharmacology , Mouth Neoplasms/pathology , SOXB1 Transcription Factors/metabolism , Squamous Cell Carcinoma of Head and Neck/pathology , Animals , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Autophagy/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/metabolism , Gefitinib/therapeutic use , Humans , Leupeptins/pharmacology , Macrolides/pharmacology , Male , Mice , Mouth Neoplasms/drug therapy , Mutagenesis , Neoplastic Stem Cells/pathology , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Protein Stability/drug effects , Proteolysis/drug effects , SOXB1 Transcription Factors/genetics , Squamous Cell Carcinoma of Head and Neck/drug therapy , Xenograft Model Antitumor AssaysABSTRACT
OBJECTIVE: This study aims to evaluate the effect of dentoalveolar distraction extraction (DDE) on site preservation, and to evaluate how the technique keeps the height and width of alveolar bones to a greater extent. METHODS: 12 beagle dogs, randomly divided into three groups (DDE group, NH group, BOG group), were used. In the dogs of three groups, the root of the left or right third mandibular premolars were respectively extracted by three methods namely, DDE, traditional extraction with natural healing, and traditional extraction with Bio-Oss bone dust implanted and guided bone regeneration (GBR). Cone-beam computed tomography (CBCT) scans and X-rays were taken immediately and three months after the tooth extraction. The height and width of the alveolar ridges were compared among different groups. RESULTS: Three months after tooth extraction, at the 1 mm level below the alveolar ridge crest, the amount and degree of buccal alveolar ridge width resorption in DDE group were significantly lower than that of NH and BOG group (P < 0.05). At the 2 mm and 3 mm level below the alveolar ridge crest, the amount and degree of buccal alveolar ridge width resorption in DDE group and BOG had no significant difference, and both were significant lower than that of NH group (P < 0.05). The height resorption of alveolar ridge in DDE group was significantly lower than NH and BOG groups (P < 0.05), while NH and BOG group had no statistically significant. CONCLUSIONS: To a greater extent, the alveolar ridge preservation through DDE could preserve the height and width of alveolar ridge crest.
