SDHB downregulation facilitates the proliferation and invasion of colorectal cancer through AMPK functions excluding those involved in the modulation of aerobic glycolysis

Xiao,Zhiming; Liu,Shaojun; Ai,Feiyan; Chen,Xiong; Li,Xiayu; Liu,Rui; Ren,Weiguo; Zhang,Xuemei; Shu,Peng; Zhang,Decai

doi:10.3892/etm.2017.5482

SDHB downregulation facilitates the proliferation and invasion of colorectal cancer through AMPK functions excluding those involved in the modulation of aerobic glycolysis

Authors:
- Zhiming Xiao
- Shaojun Liu
- Feiyan Ai
- Xiong Chen
- Xiayu Li
- Rui Liu
- Weiguo Ren
- Xuemei Zhang
- Peng Shu
- Decai Zhang
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Affiliations: Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China
Published online on: November 10, 2017 https://doi.org/10.3892/etm.2017.5482
Pages: 864-872
Copyright: © Xiao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Loss-of-function of succinate dehydrogenase‑B (SDHB) is a predisposing factor of aerobic glycolysis and cancer progression. Adenosine monophosphate activated protein kinase (AMPK) is involved in the regulation of aerobic glycolysis and the diverse hallmarks of cancer. The present study investigated whether AMPK mediated the regulatory effects of SDHB in aerobic glycolysis and cancer growth. The expression of SDHB and AMPK in colorectal cancer (CRC) and normal tissues was assessed by western blotting. HT‑29 CRC cells were used to establish in vitro models of ectopic overexpression and knockdown of SDHB. SDHB was downregulated, while AMPK and phosphorylated‑AMPK (Thr172) were upregulated in CRC tissues. Experiments involving the loss‑ or gain‑of‑function of SDHB, revealed that this protein negatively regulated AMPK by influencing its expression and activity. However, SDHB and AMPK were identified to suppress lactic acid production in CRC cells, indicating that each had an inhibitory effect on aerobic glycolysis. Therefore, the regulation of aerobic glycolysis by SDHB is unlikely to be mediated via AMPK. SDHB knockdown promoted the viability, migration and invasion of HT‑29 cells, whereas inhibition of AMPK demonstrated the opposite effect. SDHB overexpression impaired cell migration and invasion, and this effect was reversed following AMPK activation. These results indicate that AMPK may mediate the effects of SDHB in CRC cell proliferation and migration. In conclusion, SDHB downregulation in CRC cells may increase AMPK activity, which may subsequently facilitate the proliferation and invasion of these cancer cells. However, the regulation of aerobic glycolysis by SDHB may be independent of AMPK. Further studies are warranted to elucidate the mechanism by which SDHB regulates aerobic glycolysis.

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