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Review
, 2014, 461917

Hyperglycemia, a Neglected Factor During Cancer Progression

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Review

Hyperglycemia, a Neglected Factor During Cancer Progression

Wanxing Duan et al. Biomed Res Int.

Abstract

Recent evidence from large cohort studies suggests that there exists a higher cancer incidence in people with type 2 diabetes (DM2). However, to date, the potential reasons for this association remain unclear. Hyperglycemia, the most important feature of diabetes, may be responsible for the excess glucose supply for these glucose-hungry cells, and it contributes to apoptosis resistance, oncogenesis, and tumor cell resistance to chemotherapy. Considering associations between diabetes and malignancies, the effect of hyperglycemia on cancer progression in cancer patients with abnormal blood glucose should not be neglected. In this paper, we describe the role that hyperglycemia plays in cancer progression and treatment and illustrate that hyperglycemia may contribute to a more malignant phenotype of cancer cells and lead to drug resistance. Therefore, controlling hyperglycemia may have important therapeutic implications in cancer patients.

Figures

Figure 1
Figure 1
Hyperglycemia contributes to malignant cancer cell phenotypes. There is increasing evidence suggesting that there is a link between cancer and diabetes mellitus. Regardless of other shared metabolic factors, hyperglycemia, the most typical characteristic of diabetes, may be one reason to explain the prevalence of cancer incidence in patients with diabetes mellitus. Research shows that hyperglycemia may contribute to an enhanced proliferation ability, apoptosis inhibition, metastasis, perineural invasion, chemotherapy resistance, and chemotherapy intolerance.
Figure 2
Figure 2
Mechanism of high glucose-induced cellular events in cancer cells. High glucose (hyperglycemia) generates cellular ROS mainly through mitochondrial metabolism; elevated ROS activate MAPK cascade, which cause cellular events by inducing related genes transcription. In addition, high glucose can induce activation of protein kinase C (PKC) through direct and indirect pathways. It is also speculated that high glucose may induce EGF transcription and EGFR transactivation, contributing to various biological behavior of cancer cells. High glucose-mediated GDNF upregulation may also involve in different cellular events through GDNF/RET cascade.

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