PMID- 35460832
OWN - NLM
STAT- MEDLINE
DCOM- 20220603
LR  - 20220920
IS  - 1873-4847 (Electronic)
IS  - 0955-2863 (Linking)
VI  - 106
DP  - 2022 Aug
TI  - Suboptimal folic acid exposure rewires oncogenic metabolism and proteomics 
      signatures to mediate human breast cancer malignancy.
PG  - 109000
LID - S0955-2863(22)00071-7 [pii]
LID - 10.1016/j.jnutbio.2022.109000 [doi]
AB  - 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 muM; 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.
CI  - Copyright (c) 2022 Elsevier Inc. All rights reserved.
FAU - Huang, Angel
AU  - Huang A
AD  - Department of Nutritional Science, Fu Jen Catholic University, New Taipei City, 
      Taiwan.
FAU - Huang, Su-Yu
AU  - Huang SY
AD  - Department of Nutritional Science, Fu Jen Catholic University, New Taipei City, 
      Taiwan.
FAU - Shah, Pramod
AU  - Shah P
AD  - Department of Nutritional Science, Fu Jen Catholic University, New Taipei City, 
      Taiwan.
FAU - Ku, Wei-Chi
AU  - Ku WC
AD  - School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei 
      City, Taiwan.
FAU - Huang, Kuang-Ta
AU  - Huang KT
AD  - Ph.D. Program in Nutrition and Food Science, Fu Jen Catholic University, New 
      Taipei City, Taiwan.
FAU - Liu, Yi-Fang
AU  - Liu YF
AD  - Department of Nutritional Science, Fu Jen Catholic University, New Taipei City, 
      Taiwan.
FAU - Su, Chun-Li
AU  - Su CL
AD  - Graduate Program of Nutrition Science, School of Life Science, National Taiwan 
      Normal University, Taiwan.
FAU - Huang, Rwei-Fen S
AU  - Huang RS
AD  - Department of Nutritional Science, Fu Jen Catholic University, New Taipei City, 
      Taiwan; Ph.D. Program in Nutrition and Food Science, Fu Jen Catholic University, 
      New Taipei City, Taiwan. Electronic address: 034825@mail.fju.edu.tw.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220420
PL  - United States
TA  - J Nutr Biochem
JT  - The Journal of nutritional biochemistry
JID - 9010081
RN  - 935E97BOY8 (Folic Acid)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - *Breast Neoplasms
MH  - Carcinogenesis
MH  - Female
MH  - *Folic Acid/pharmacology
MH  - Humans
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Proteomics
MH  - TOR Serine-Threonine Kinases/metabolism
OTO - NOTNLM
OT  - folic acid
OT  - human breast cancers
OT  - malignancy transformation
OT  - oncogenic metabolism
OT  - proteomic signatures
EDAT- 2022/04/24 06:00
MHDA- 2022/06/07 06:00
CRDT- 2022/04/23 20:09
PHST- 2021/06/05 00:00 [received]
PHST- 2021/11/25 00:00 [revised]
PHST- 2022/02/22 00:00 [accepted]
PHST- 2022/04/24 06:00 [pubmed]
PHST- 2022/06/07 06:00 [medline]
PHST- 2022/04/23 20:09 [entrez]
AID - S0955-2863(22)00071-7 [pii]
AID - 10.1016/j.jnutbio.2022.109000 [doi]
PST - ppublish
SO  - J Nutr Biochem. 2022 Aug;106:109000. doi: 10.1016/j.jnutbio.2022.109000. Epub 
      2022 Apr 20.