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

Liu, Tsung-Yun; Chang, Wan-Jung; Chen, Chang-Yi; Sun, Fang-Ju; Cheng, Hui-Wen; Chen, Tzong-Yueh; Lin, Shu Chun; Li, Wan Chun

doi:10.18632/oncotarget.4922

Cited by 20 publications

(26 citation statements)

References 72 publications

(26 reference statements)

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“…All experimental reagents including 4-nitroquinoline 1-oxide (4-NQO), 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), cisplatin (CDDP), and 5-fluorouracil (5-FU) were purchased from Sigma. The HNSCC cell lines, clinical human HNSCC tissues, and animal procedure were obtained and described elsewhere (60,61).…”

Section: Basic Reagents Cells and Animal And Human Protocolsmentioning

confidence: 99%

Regulatory Role of Hexokinase 2 in Modulating Head and Neck Tumorigenesis

Huang

Hsieh

et al. 2020

Front. Oncol.Has correction 2020-3-31 Has erratum 2020-3-31

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To support great demand of cell growth, cancer cells preferentially obtain energy and biomacromolecules by glycolysis over mitochondrial oxidative phosphorylation (OxPhos). Among all glycolytic enzymes, hexokinase (HK), a rate-limiting enzyme at the first step of glycolysis to catalyze cellular glucose into glucose-6-phosphate, is herein emphasized. Four HK isoforms, HK1-HK4, were discovered in nature. It was shown that HK2 expression is enriched in many tumor cells and correlated with poorer survival rates in most neoplastic cells. HK2-mediated regulations for cell malignancy and mechanistic cues in regulating head and neck tumorigenesis, however, are not fully elucidated. Cellular malignancy index, such as cell growth, cellular motility, and treatment sensitivity, and molecular alterations were determined in HK2-deficient head and neck squamous cell carcinoma (HNSCC) cells. By using various cancer databases, HK2, but not HK1, positively correlates with HNSCC progression in a stage-dependent manner. A high HK2 expression was detected in head and neck cancerous tissues compared with their normal counterparts, both in mouse and human subjects. Loss of HK2 in HNSCC cells resulted in reduced cell (in vitro) and tumor (in vivo) growth, as well as decreased epithelial-mesenchymal transition-mediated cell movement; in contrast, HK2-deficient HNSCC cells exhibited greater sensitivity to chemotherapeutic drugs cisplatin and 5-fluorouracil but are more resistant to photodynamic therapy, indicating that HK2 expression could selectively define treatment sensitivity in HNSCC cells. At the molecular level, it was found that HK2 alteration drove metabolic reprogramming toward OxPhos and modulated oncogenic Akt and mutant TP53-mediated signals in HNSCC cells. In summary, the present study showed that HK2 suppression could lessen HNSCC oncogenicity and modulate therapeutic sensitivity, thereby being an ideal therapeutic target for HNSCCs.

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Section: Basic Reagents Cells and Animal And Human Protocolsmentioning

confidence: 99%

Regulatory Role of Hexokinase 2 in Modulating Head and Neck Tumorigenesis

Huang

Hsieh

et al. 2020

Front. Oncol.Has correction 2020-3-31 Has erratum 2020-3-31

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“…In this respect, a recent in vitro study with different HNSCC cells demonstrated that overdosed glucose promoted HNSCC malignancy in the time‐course manner. Mechanisms involved include modulation of cell growth, inhibition of cell differentiation, enhanced cell motility, increased drug resistance, and upregulation of nutrient‐mediated oncogenic pathways . However, in this work, we have not carried out any mechanistic studies, and, therefore, further studies are needed to explain the behavior of these tumors under glycemic dysregulation pressure.…”

Section: Discussionmentioning

confidence: 99%

“…Although some epidemiological studies of published trials suggest that there is a significant association between T2DM and an increased risk of cancer, the results are often contradictory . The inconsistent results from previous studies might be due to a lack of adjustment for identical aging and other associated confounders, and inaccessibility of biochemical parameters (such as blood glucose level and HbA1c) during analysis.…”

Section: Discussionmentioning

confidence: 99%

“…The presence of confounders might lead to difficulty in correlating precisely the T2DM pathology with HNSCC development . Stott‐Miller et al investigated whether T2DM or metabolic syndrome were associated with HNSCC.…”

Section: Discussionmentioning

confidence: 99%

“…In our study, the association between the HOMA‐IR and outcome was independent of the presence of diabetes, which highlights the role of insulin resistance in the development of HNSCC and the response to treatment. It has been reported that proper glucose control leads to better clinical outcomes in patients with breast cancer, highlighting the need to tightly control blood glucose in patients with T2DM who have neoplastic lesions . The categorized pretreatment profile might, therefore, be more useful than other classifications because a patient with a good control of their diabetes might have normal glucose and/or insulin levels.…”

Section: Discussionmentioning

confidence: 99%

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