Research Papers:

Dynamic cellular and molecular modulations of diabetes mediated head and neck carcinogenesis

Chung-Ji Liu, Wan-Jung Chang, Chang-Yi Chen, Fang-Ju Sun, Hui-Wen Cheng, Tsai-Ying Chen, Shu-Chun Lin and Wan-Chun Li _

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Oncotarget. 2015; 6:29268-29284. https://doi.org/10.18632/oncotarget.4922

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Chung-Ji Liu1,2,4,*, Wan-Jung Chang4,*, Chang-Yi Chen4, Fang-Ju Sun2,3, Hui-Wen Cheng2, Tsai-Ying Chen4, Shu-Chun Lin4,5, Wan-Chun Li4

1Department of Oral and Maxillofacial Surgery, MacKay Memorial Hospital, Taipei, Taiwan

2Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan

3Mackay College of Medicine, Nursing and Management, Taipei, Taiwan

4Institute of Oral Biology and Department of Dentistry, School of Dentistry, National Yang-Ming University, Taipei, Taiwan

5Department of Stomatology, Taipei Veterans General Hospital, Taipei, Taiwan

*These authors have contributed equally to this work

Correspondence to:

Wan-Chun Li, e-mail: [email protected]

Keywords: cell malignancy, diabetes mellitus, head and neck cancer, lymph node metastasis, prognosis

Received: March 31, 2015     Accepted: August 11, 2015     Published: August 21, 2015


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.

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