Breast Cancer with Increased Drug Resistance, Invasion Ability, and Cancer Stem Cell Properties through Metabolism Reprogramming.
Breast Cancer with Increased Drug Resistance, Invasion Ability, and Cancer Stem Cell Properties through Metabolism Reprogramming.
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DOI：
10.3390/ijms232112875
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发表时间：
2022-10-25
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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作者：
乳腺癌是一种异质性疾病，乳腺癌患者的生存率在很大程度上取决于其分期和临床病理特征。放化疗是提高晚期乳腺癌患者生存率的常用方法。然而，治疗过程往往伴随着耐药性的产生，最终导致治疗失败。代谢重编程已被认为是乳腺癌耐药的一种机制。在本研究中，我们通过一系列的长期阿霉素体外处理建立了一个阿霉素耐药的MCF-7（MCF-7-D500）细胞系。我们的数据显示，与亲代细胞相比，MCF-7-D500细胞表现出增加的多药耐药性、癌症干性和侵袭性。我们通过液相色谱-质谱分析了MCF-7和MCF-7-D500细胞的代谢谱。我们观察到25种代谢物的显著变化，其中，在具有阿霉素抗性的MCF-7细胞中，21种表现出水平增加（>1.5倍变化和p <0.05），4种表现出水平降低（<0.75倍变化和p < 0.05）。这些结果表明代谢重编程参与乳腺癌耐药的发展，特别是糖酵解，三羧酸（TCA）循环和六胺生物合成途径（HBP）的激活。此外，大多数参与糖酵解、HBP和TCA循环的酶在MCF-7-D500细胞中上调，导致乳腺癌患者预后不良。我们的研究结果为乳腺癌耐药的调控提供了新的见解，这些耐药相关的代谢途径可以作为乳腺癌耐药治疗的靶点。
Breast cancer is a heterogeneous disease, and the survival rate of patients with breast cancer strongly depends on their stage and clinicopathological features. Chemoradiation therapy is commonly employed to improve the survivability of patients with advanced breast cancer. However, the treatment process is often accompanied by the development of drug resistance, which eventually leads to treatment failure. Metabolism reprogramming has been recognized as a mechanism of breast cancer resistance. In this study, we established a doxorubicin-resistant MCF-7 (MCF-7-D500) cell line through a series of long-term doxorubicin in vitro treatments. Our data revealed that MCF-7-D500 cells exhibited increased multiple-drug resistance, cancer stemness, and invasiveness compared with parental cells. We analyzed the metabolic profiles of MCF-7 and MCF-7-D500 cells through liquid chromatography–mass spectrometry. We observed significant changes in 25 metabolites, of which, 21 exhibited increased levels (>1.5-fold change and p < 0.05) and 4 exhibited decreased levels (<0.75-fold change and p < 0.05) in MCF-7 cells with doxorubicin resistance. These results suggest the involvement of metabolism reprogramming in the development of drug resistance in breast cancer, especially the activation of glycolysis, the tricarboxylic acid (TCA) cycle, and the hexamine biosynthesis pathway (HBP). Furthermore, most of the enzymes involved in glycolysis, the HBP, and the TCA cycle were upregulated in MCF-7-D500 cells and contributed to the poor prognosis of patients with breast cancer. Our findings provide new insights into the regulation of drug resistance in breast cancer, and these drug resistance-related metabolic pathways can serve as targets for the treatment of chemoresistance in breast cancer.
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DOI：
10.1073/pnas.2011342118
发表时间：
2021-01-19
影响因子：
11.1
作者：
Damaghi M;West J;Robertson-Tessi M;Xu L;Ferrall-Fairbanks MC;Stewart PA;Persi E;Fridley BL;Altrock PM;Gatenby RA;Sims PA;Anderson ARA;Gillies RJ
通讯作者：
Gillies RJ
影响因子：
13.8
作者：
Liberti MV;Locasale JW
通讯作者：
Locasale JW
DOI：
10.3390/molecules27061762
发表时间：
2022-03-08
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Cha HK;Cheon S;Kim H;Lee KM;Ryu HS;Han D
通讯作者：
Han D
影响因子：
28.2
作者：
Cantor JR;Sabatini DM
通讯作者：
Sabatini DM
影响因子：
254.7
作者：
DeSantis, Carol;Ma, Jiemin;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin