SDHB downregulation facilitates the proliferation and invasion of colorectal cancer through AMPK functions excluding those involved in the modulation of aerobic glycolysis.
SDHB downregulation facilitates the proliferation and invasion of colorectal cancer through AMPK functions excluding those involved in the modulation of aerobic glycolysis.
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SDHB 下调通过 AMPK 功能（不包括参与有氧糖酵解调节的功能）促进结直肠癌的增殖和侵袭
DOI：
10.3892/etm.2017.5482
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发表时间：
2018-01
影响因子：
2.7
通讯作者：
Zhang D
中科院分区：
文献类型：
--
作者：
Xiao Z;Liu S;Ai F;Chen X;Li X;Liu R;Ren W;Zhang X;Shu P;Zhang D
琥珀酸脱氢酶 B (SDHB) 功能丧失是有氧糖酵解和癌症进展的诱发因素。单磷酸腺苷激活蛋白激酶 (AMPK) 参与有氧糖酵解和癌症的多种特征的调节。本研究调查了 AMPK 是否介导 SDHB 在有氧糖酵解和癌症生长中的调节作用。通过蛋白质印迹法评估结直肠癌 (CRC) 和正常组织中 SDHB 和 AMPK 的表达。使用HT-29 CRC细胞建立SDHB异位过表达和敲低的体外模型。在 CRC 组织中，SDHB 下调，而 AMPK 和磷酸化 AMPK (Thr172) 上调。涉及 SDHB 功能丧失或获得的实验表明，该蛋白通过影响 AMPK 的表达和活性来负向调节 AMPK。然而，SDHB 和 AMPK 被发现可以抑制 CRC 细胞中的乳酸产生，这表明它们各自对有氧糖酵解具有抑制作用。因此，SDHB 对有氧糖酵解的调节不太可能是通过 AMPK 介导的。 SDHB 敲低促进 HT-29 细胞的活力、迁移和侵袭，而 AMPK 抑制则表现出相反的效果。 SDHB 过度表达会损害细胞迁移和侵袭，并且这种效应在 AMPK 激活后被逆转。这些结果表明 AMPK 可能介导 SDHB 对 CRC 细胞增殖和迁移的影响。总之，CRC 细胞中 SDHB 下调可能会增加 AMPK 活性，从而促进这些癌细胞的增殖和侵袭。然而，SDHB 对有氧糖酵解的调节可能独立于 AMPK。需要进一步的研究来阐明 SDHB 调节有氧糖酵解的机制。
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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