Dynamic cellular and molecular modulations of diabetes mediated head and neck carcinogenesis.
Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent neoplasms worldwide. While numerous potent dietary insults were considered as oncogenic players for HNSCC development, the impact of metabolic imbalance was less emphasized during HNSCC carcinogenesis. Previous preclinical and epidemiological investigations showed that DM could possibly be correlated with greater incidence and poorer prognosis in HNSCC patients; however, the outcomes from different groups are contradictive and underlying mechanisms remains elusive. In the present study, the changes of cellular malignancy in response to prolonged glucose incubation in HNSCC cells were examined. The results demonstrated that hyperglycemia enhanced HNSCC cell malignancy over time through suppression of cell differentiation, promotion of cell motility, increased resistance to cisplatin, and up-regulation of the nutrient-sensing Akt/AMPK-mTORC1 pathway. Further analysis showed that a more aggressive tongue neoplastic progression was found under DM conditions compared to non-DM state whereas DM pathology led to a higher percentage of cervical lymph node metastasis and poorer prognosis in HNSCC patients. Taken together, the present study confirms that hyperglycemia and DM could enhance HNSCC malignancy and the outcomes are of great benefit in providing better anti-cancer treatment strategy for DM patients with HNSCC.
Department of Oral and Maxillofacial Surgery, MacKay Memorial Hospital, Taipei, Taiwan.|Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan.|Institute of Oral Biology and Department of Dentistry, School of Dentistry, National Yang-Ming University, Taipei, Taiwan.
Chung-Ji
CJ
Liu
Institute of Oral Biology and Department of Dentistry, School of Dentistry, National Yang-Ming University, Taipei, Taiwan.
Wan-Jung
WJ
Chang
Institute of Oral Biology and Department of Dentistry, School of Dentistry, National Yang-Ming University, Taipei, Taiwan.
Chang-Yi
CY
Chen
Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan.|Mackay College of Medicine, Nursing and Management, Taipei, Taiwan.
Fang-Ju
FJ
Sun
Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan.
Hui-Wen
HW
Cheng
Institute of Oral Biology and Department of Dentistry, School of Dentistry, National Yang-Ming University, Taipei, Taiwan.
Tsai-Ying
TY
Chen
Institute of Oral Biology and Department of Dentistry, School of Dentistry, National Yang-Ming University, Taipei, Taiwan.|Department of Stomatology, Taipei Veterans General Hospital, Taipei, Taiwan.
Shu-Chun
SC
Lin
Institute of Oral Biology and Department of Dentistry, School of Dentistry, National Yang-Ming University, Taipei, Taiwan.
Wan-Chun
WC
Li
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000328:Adult; D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002945:Cisplatin / Q000494:pharmacology; D003599:Cytoskeleton / Q000378:metabolism; D048909:Diabetes Complications / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D046912:Multiprotein Complexes / Q000378:metabolism; D016016:Proportional Hazards Models; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012189:Retrospective Studies; D012307:Risk Factors; D015398:Signal Transduction; D000077195:Squamous Cell Carcinoma of Head and Neck; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D046912:Multiprotein Complexes; D000076222:Mechanistic Target of Rapamycin Complex 1; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D005947:Glucose; D002945:Cisplatin
cell malignancy; diabetes mellitus; head and neck cancer; lymph node metastasis; prognosis