Suboptimal folic acid exposure rewires oncogenic metabolism and proteomics signatures to mediate human breast cancer malignancy

Angel Huang, Su Yu Huang, Pramod Shah, Wei Chi Ku, Kuang Ta Huang, Yi Fang Liu, Chun Li Su, Rwei Fen S. Huang*

*此作品的通信作者

研究成果: 雜誌貢獻期刊論文同行評審

摘要

Whether treatment with folic acid (FA) affects human breast cancer positively or negatively remains unclear. We subjected human Michigan Cancer Foundation-7 cells, a human breast cancer cell line, to suboptimal FA at low levels (10 nM; LF) and high levels (50 μM; HF) and investigated the molecular mechanisms underlying their effects through metabolic flux and systematic proteomics analyses. The data indicated that LF induced and HF aggravated 2-fold higher mitochondrial toxicity in terms of suppressed oxidative respiration, increased fermented glycolysis, and enhanced anchorage-independent oncospheroid formation. Quantitative proteomics and Gene Ontology enrichment analysis were used to profile LF- and HF-altered proteins involved in metabolism, apoptosis, and malignancy pathways. Through STRING analysis, we identified a connection network between LF- and HF-altered proteins with mammalian target of rapamycin (mTOR). Rapamycin-induced blockage of mTOR complex 1 (mTORC1) signaling, which regulates metabolism, differentially inhibited LF- and HF-modulated protein signatures of mitochondrial NADH dehydrogenase ubiquinone flavoprotein 2, mitochondrial glutathione peroxidase 4, kynureninase, and alpha-crystallin B chain as well as programmed cell death 5 in transcript levels; it subsequently diminished apoptosis and oncospheroid formation in LF/HF-exposed cells. Taken together, our data indicate that suboptimal FA treatment rewired oncogenic metabolism and mTORC1-mediated proteomics signatures to promote breast cancer development.

原文英語
文章編號109000
期刊Journal of Nutritional Biochemistry
106
DOIs
出版狀態已發佈 - 2022 8月

ASJC Scopus subject areas

  • 內分泌學、糖尿病和代謝
  • 生物化學
  • 分子生物學
  • 營養與營養學
  • 臨床生物化學

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