PMID- 36419896
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221125
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 12
DP  - 2022
TI  - 17-beta Estradiol up-regulates energy metabolic pathways, cellular proliferation and 
      tumor invasiveness in ER+ breast cancer spheroids.
PG  - 1018137
LID - 10.3389/fonc.2022.1018137 [doi]
LID - 1018137
AB  - Several biological processes related to cancer malignancy are regulated by 17-beta 
      estradiol (E2) in ER+-breast cancer. To establish the role of E2 on the atypical 
      cancer energy metabolism, a systematic study analyzing transcription factors, 
      proteins, and fluxes associated with energy metabolism was undertaken in 
      multicellular tumor spheroids (MCTS) from human ER+ MCF-7 breast cancer cells. At 
      E2 physiological concentrations (10 and 100 nM for 24 h), both ERalpha and ERbeta 
      receptors, and their protein target pS2, increased by 0.6-3.5 times vs. 
      non-treated MCTS, revealing an activated E2/ER axis. E2 also increased by 30-470% 
      the content of several transcription factors associated to mitochondrial 
      biogenesis and oxidative phosphorylation (OxPhos) (p53, PGC1-alpha) and glycolytic 
      pathways (HIF1-alpha, c-MYC). Several OxPhos and glycolytic proteins (36-257%) as 
      well as pathway fluxes (48-156%) significantly increased being OxPhos the 
      principal ATP cellular supplier (>75%). As result of energy metabolism 
      stimulation by E2, cancer cell migration and invasion processes and related 
      proteins (SNAIL, FN, MM-9) contents augmented by 24-189% vs. non-treated MCTS. 
      Celecoxib at 10 nM blocked OxPhos (60%) as well as MCTS growth, cell migration 
      and invasiveness (>40%); whereas the glycolytic inhibitor iodoacetate (0.5 microM) 
      and doxorubicin (70 nM) were innocuous. Our results show for the first time using 
      a more physiological tridimensional cancer model, resembling the initial stages 
      of solid tumors, that anti-mitochondrial therapy may be useful to deter 
      hormone-dependent breast carcinomas.
CI  - Copyright (c) 2022 Pacheco-Velazquez, Ortega-Mejia, Vargas-Navarro, Padilla-Flores, 
      Robledo-Cadena, Tapia-Martinez, Penalosa-Castro, Aguilar-Ponce, Granados-Rivas, 
      Moreno-Sanchez and Rodriguez-Enriquez.
FAU - Pacheco-Velazquez, Silvia Cecilia
AU  - Pacheco-Velazquez SC
AD  - Departamento de Bioquimica, Instituto Nacional de Cardiologia, Ciudad de Mexico, 
      Mexico.
FAU - Ortega-Mejia, Ingrid Itzayanna
AU  - Ortega-Mejia II
AD  - Departamento de Bioquimica, Instituto Nacional de Cardiologia, Ciudad de Mexico, 
      Mexico.
FAU - Vargas-Navarro, Jorge Luis
AU  - Vargas-Navarro JL
AD  - Departamento de Bioquimica, Instituto Nacional de Cardiologia, Ciudad de Mexico, 
      Mexico.
FAU - Padilla-Flores, Joaquin Alberto
AU  - Padilla-Flores JA
AD  - Departamento de Bioquimica, Instituto Nacional de Cardiologia, Ciudad de Mexico, 
      Mexico.
FAU - Robledo-Cadena, Diana Xochiquetzal
AU  - Robledo-Cadena DX
AD  - Departamento de Bioquimica, Instituto Nacional de Cardiologia, Ciudad de Mexico, 
      Mexico.
FAU - Tapia-Martinez, Gabriela
AU  - Tapia-Martinez G
AD  - Departamento de Bioquimica, Instituto Nacional de Cardiologia, Ciudad de Mexico, 
      Mexico.
FAU - Penalosa-Castro, Ignacio
AU  - Penalosa-Castro I
AD  - Laboratorio de Control Metabolico, Carrera de Biologia, Facultad de Estudios 
      Superiores Iztacala, Universidad Nacional Autonoma de Mexico, Los Reyes Ixtacala, 
      Hab, Tlalnepantla, Mexico.
FAU - Aguilar-Ponce, Jose Luis
AU  - Aguilar-Ponce JL
AD  - Hospital Medica Sur, Area de Oncologia, Ciudad de Mexico, Mexico.
FAU - Granados-Rivas, Juan Carlos
AU  - Granados-Rivas JC
AD  - Laboratorio de Control Metabolico, Carrera de Medicina, Facultad de Estudios 
      Superiores Iztacala, Universidad Nacional Autonoma de Mexico, Los Reyes Ixtacala, 
      Hab, Tlalnepantla, Mexico.
FAU - Moreno-Sanchez, Rafael
AU  - Moreno-Sanchez R
AD  - Laboratorio de Control Metabolico, Carrera de Biologia, Facultad de Estudios 
      Superiores Iztacala, Universidad Nacional Autonoma de Mexico, Los Reyes Ixtacala, 
      Hab, Tlalnepantla, Mexico.
FAU - Rodriguez-Enriquez, Sara
AU  - Rodriguez-Enriquez S
AD  - Departamento de Bioquimica, Instituto Nacional de Cardiologia, Ciudad de Mexico, 
      Mexico.
AD  - Laboratorio de Control Metabolico, Carrera de Medicina, Facultad de Estudios 
      Superiores Iztacala, Universidad Nacional Autonoma de Mexico, Los Reyes Ixtacala, 
      Hab, Tlalnepantla, Mexico.
LA  - eng
PT  - Journal Article
DEP - 20221107
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC9676491
OTO - NOTNLM
OT  - 17-beta estradiol
OT  - ER+ breast cancer
OT  - OxPhos
OT  - anti-mitochondrial therapy
OT  - glycolysis
OT  - metastasis
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/11/25 06:00
MHDA- 2022/11/25 06:01
PMCR- 2022/01/01
CRDT- 2022/11/24 02:27
PHST- 2022/08/12 00:00 [received]
PHST- 2022/10/18 00:00 [accepted]
PHST- 2022/11/24 02:27 [entrez]
PHST- 2022/11/25 06:00 [pubmed]
PHST- 2022/11/25 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2022.1018137 [doi]
PST - epublish
SO  - Front Oncol. 2022 Nov 7;12:1018137. doi: 10.3389/fonc.2022.1018137. eCollection 
      2022.