Metabolic rewiring is associated with HPV-specific profiles in cervical cancer cell lines.

Metabolic rewiring is associated with HPV-specific profiles in cervical cancer cell lines.
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DOI:
10.1038/s41598-021-96038-8
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发表时间:
2021-09-06
期刊:
影响因子:
4.6
通讯作者:
Anagnou NP
Anagnou NP
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Pappa KI;Daskalakis G;Anagnou NP

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HPV阳性和HPV阴性的宫颈癌都与代谢异常有关,尽管致癌因素仍然难以捉摸。在这里,我们展示了四个不同的宫颈细胞系,一个正常细胞系和三个癌细胞系,一个HPV阴性(C33A)和两个HPV阳性(SiHA HPV16+,HeLa HPV18+)的代谢谱,使用超高效液相色谱和高分辨率质谱仪进行评估。在总共462种代谢物中,248到326种表现出统计上的显著差异,而随机森林分析为每种细胞系确定了独特的分子。这两个HPV+细胞系表现出Warburg代谢的特征,与HPVE6蛋白的作用一致。SIHA和HeLa细胞显示了嘌呤挽救途径的活性,而C33A细胞通过一种新的机制显示了胞苷的合成。这些数据记录了发生在宫颈癌中的高度动态的HPV特异性代谢途径的重新连接。因此,这种方法最终可以为宫颈癌的发生提供新的机制见解。
Both HPV-positive and HPV-negative cervical cancers are associated with aberrant metabolism, although the oncogenic drivers remain elusive. Here we show the assessment of the metabolomic profiles of four distinct cervical cell lines, a normal and three cancer cell lines, one HPV-negative (C33A) and two HPV-positive (SiHa HPV16+, HeLa HPV18+), employing an ultra performance liquid chromatography and a high resolution mass spectrometry. Out of the total 462 metabolites, 248 to 326 exhibited statistically significant differences, while Random Forests analysis identified unique molecules for each cell line. The two HPV+ cell lines exhibited features of Warburg metabolism, consistent with the role of the HPV E6 protein. SiHa and HeLa cells displayed purine salvage pathway activity, while C33A cells revealed synthesis of cytidine, via a novel mechanism. These data document a highly dynamic HPV-specific rewiring of metabolic pathways occurring in cervical cancer. Therefore, this approach can eventually provide novel mechanistic insights into cervical carcinogenesis.
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