PMID- 31229911
OWN - NLM
STAT- MEDLINE
DCOM- 20201104
LR  - 20201104
IS  - 1873-4847 (Electronic)
IS  - 0955-2863 (Linking)
VI  - 70
DP  - 2019 Aug
TI  - VD(3) mitigates breast cancer aggressiveness by targeting V-H(+)-ATPase.
PG  - 185-193
LID - S0955-2863(19)30155-X [pii]
LID - 10.1016/j.jnutbio.2019.05.005 [doi]
AB  - Low vitamin D levels increase the risk of developing several cancer types 
      including breast cancer. Breast cancer is the most incident cancer among women 
      worldwide and in the United States. Our previous study showed that vitamin D 
      (VD(3)) decreases breast cancer aggressiveness by inhibiting mammalian target of 
      rapamycin (mTOR). However, the full mechanism underlying VD(3) effects in breast 
      cancer, including some activators of mTORC1, is yet to be explored. Metastatic 
      cancer cells overexpress the V-H(+)-ATPase proton pump at the plasma membrane to 
      maintain the optimal pH to sustain cancer growth promoting their own invasion and 
      metastasis by acidifying the extracellular environment. Among its other roles, 
      V-H(+)-ATPase overexpression and activity are associated with high glycolytic 
      flux, mTORC1 activation, and hypoxia. V-H(+)-ATPase's role in mTORC1 activation 
      and glycolytic metabolism supports our hypothesis that VD(3), a nontoxic and 
      widely used compound, inhibits the proton pump resulting in a significant 
      decrease in cancer aggressiveness. VD(3) and the specific inhibitor bafilomycin 
      A(1) (positive control) profoundly inhibit V-H(+)-ATPase function and expression. 
      Highly metastatic MB231 has more pronounced effects (high extracellular pH, low 
      migration speed and changes in cell mechanics) than lowly metastatic MCF-7 due to 
      the higher expression of V-H(+)-ATPase, which drives the more aggressive 
      phenotype. Our data show, for the first time, that VD(3) strongly inhibited 
      V-H(+)-ATPase function and expression in breast cancer cells, thereby suggesting 
      its use as a possible therapeutic agent.
CI  - Published by Elsevier Inc.
FAU - Santos, Julianna M
AU  - Santos JM
AD  - Chemical Engineering Mechanical Engineering Department, Texas Tech University, 
      Lubbock, TX, USA.
FAU - Hussain, Fazle
AU  - Hussain F
AD  - Chemical Engineering Mechanical Engineering Department, Texas Tech University, 
      Lubbock, TX, USA; Internal Medicine, Cell Physiology and Molecular Biophysics, 
      TTUHSC, Lubbock, TX, USA. Electronic address: fazle.hussain@ttu.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190525
PL  - United States
TA  - J Nutr Biochem
JT  - The Journal of nutritional biochemistry
JID - 9010081
RN  - 0 (Actins)
RN  - 1406-16-2 (Vitamin D)
RN  - 1C6V77QF41 (Cholecalciferol)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 3.6.3.14 (Proton-Translocating ATPases)
SB  - IM
MH  - Actins/metabolism
MH  - Breast Neoplasms/*enzymology
MH  - Cell Line, Tumor
MH  - Cell Movement
MH  - Cholecalciferol/*metabolism
MH  - Female
MH  - *Gene Expression Regulation, Enzymologic
MH  - *Gene Expression Regulation, Neoplastic
MH  - Glycolysis
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Hypoxia/metabolism
MH  - MCF-7 Cells
MH  - Mechanistic Target of Rapamycin Complex 1/metabolism
MH  - Neoplasm Invasiveness
MH  - Neoplasm Metastasis
MH  - Proton-Translocating ATPases/*metabolism
MH  - Vitamin D
OTO - NOTNLM
OT  - Breast cancer
OT  - Cell mechanics
OT  - Cell migration
OT  - V-H(+)-ATPase
OT  - VD(3)
OT  - pH
EDAT- 2019/06/24 06:00
MHDA- 2020/11/05 06:00
CRDT- 2019/06/24 06:00
PHST- 2019/02/15 00:00 [received]
PHST- 2019/04/26 00:00 [revised]
PHST- 2019/05/10 00:00 [accepted]
PHST- 2019/06/24 06:00 [pubmed]
PHST- 2020/11/05 06:00 [medline]
PHST- 2019/06/24 06:00 [entrez]
AID - S0955-2863(19)30155-X [pii]
AID - 10.1016/j.jnutbio.2019.05.005 [doi]
PST - ppublish
SO  - J Nutr Biochem. 2019 Aug;70:185-193. doi: 10.1016/j.jnutbio.2019.05.005. Epub 
      2019 May 25.