SIPA1 Enhances Aerobic Glycolysis Through HIF-2α Pathway to Promote Breast Cancer Metastasis.
SIPA1 Enhances Aerobic Glycolysis Through HIF-2α Pathway to Promote Breast Cancer Metastasis.
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SIPA1通过HIF-2α途径增强有氧糖酵解促进乳腺癌转移
DOI：
10.3389/fcell.2021.779169
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发表时间：
2021
影响因子：
5.5
通讯作者：
Su L
中科院分区：
文献类型：
--
作者：
Yao C;Weng J;Feng L;Zhang W;Xu Y;Zhang P;Tanaka Y;Su L
增加对有氧糖酵解的依赖是大多数癌细胞的特征，然而在环境氧条件下促进转移性乳腺癌细胞有氧糖酵解的机制尚不清楚。在这里，我们证明了信号诱导增殖相关1 （SIPA1）的异常表达增强了乳腺癌细胞的有氧糖酵解，并改变了ATP产生的主要来源，从氧化磷酸化到糖酵解。我们发现SIPA1可以促进编码缺氧诱导因子-2α (HIF-2α)的基因EPAS1的转录，并上调多个糖酵解相关基因的表达，从而增加有氧糖酵解。我们还发现，通过抑制SIPA1表达或草酸盐治疗来阻断有氧糖酵解，在体外和体内均可抑制乳腺癌细胞的肿瘤转移。综上所述，SIPA1的异常表达导致即使在环境氧水平下葡萄糖代谢也从氧化磷酸化转变为有氧糖酵解，这可能会加重乳腺癌细胞的恶性。目前的研究结果提示了SIPA1表达失调的乳腺癌治疗方法的潜在靶点。
Increased dependence on aerobic glycolysis is characteristic of most cancer cells, whereas the mechanism underlying the promotion of aerobic glycolysis in metastatic breast cancer cells under ambient oxygen has not been well understood. Here, we demonstrated that aberrant expression of signal-induced proliferation-associated 1 (SIPA1) enhanced aerobic glycolysis and altered the main source of ATP production from oxidative phosphorylation to glycolysis in breast cancer cells. We revealed that SIPA1 promoted the transcription of EPAS1, which is known as the gene encoding hypoxia-inducible factor-2α (HIF-2α) and up-regulated the expression of multiple glycolysis-related genes to increase aerobic glycolysis. We also found that blocking aerobic glycolysis by either knocking down SIPA1 expression or oxamate treatment led to the suppression of tumor metastasis of breast cancer cells both in vitro and in vivo. Taken together, aberrant expression of SIPA1 resulted in the alteration of glucose metabolism from oxidative phosphorylation to aerobic glycolysis even at ambient oxygen levels, which might aggravate the malignancy of breast cancer cells. The present findings indicate a potential target for the development of therapeutics against breast cancers with dysregulated SIPA1 expression.
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DOI：
10.1186/bcr3415
发表时间：
2013-04-19
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Riaz M;van Jaarsveld MT;Hollestelle A;Prager-van der Smissen WJ;Heine AA;Boersma AW;Liu J;Helmijr J;Ozturk B;Smid M;Wiemer EA;Foekens JA;Martens JW
通讯作者：
Martens JW
影响因子：
4.8
作者：
Lu, Xin;Bennet, Bryson;Kang, Yibin
通讯作者：
Kang, Yibin
DOI：
10.1016/j.neo.2015.08.005
发表时间：
2015-08
期刊：
Neoplasia (New York, N.Y.)
影响因子：
--
作者：
Simões RV;Serganova IS;Kruchevsky N;Leftin A;Shestov AA;Thaler HT;Sukenick G;Locasale JW;Blasberg RG;Koutcher JA;Ackerstaff E
通讯作者：
Ackerstaff E
影响因子：
5.4
作者：
Chen, Dongru;Wu, Liping;Deng, Jianqing
通讯作者：
Deng, Jianqing
三阴性乳腺癌细胞的代谢分析揭示了代谢脆弱性。
影响因子：
5.9
作者：
Lanning NJ;Castle JP;Singh SJ;Leon AN;Tovar EA;Sanghera A;MacKeigan JP;Filipp FV;Graveel CR
通讯作者：
Graveel CR