PMID- 27121619
OWN - NLM
STAT- MEDLINE
DCOM- 20180206
LR  - 20190221
IS  - 1557-9077 (Electronic)
IS  - 1050-7256 (Linking)
VI  - 26
IP  - 7
DP  - 2016 Jul
TI  - 5'-AMP-Activated Protein Kinase Regulates Papillary (TPC-1 and BCPAP) Thyroid 
      Cancer Cell Survival, Migration, Invasion, and Epithelial-to-Mesenchymal 
      Transition.
PG  - 933-42
LID - 10.1089/thy.2015.0440 [doi]
AB  - BACKGROUND: Differentiated thyroid carcinomas (DTC) are associated with a good 
      prognosis and a high survival rate. However, tumor recurrence occurs in 
      approximately 20-30% of DTC patients, reinforcing the importance of identifying 
      new molecular targets for cancer management. It has been shown that the 
      5'-AMP-activated protein kinase (AMPK) is over-activated in papillary thyroid 
      cancer (PTC). This study aimed to investigate the effects of 
      5-aminoimidazole-4-carboxamide-ribonucleoside (AICAR), an AMPK activator, on 
      various aspects of thyroid cancer cell behavior, including cell survival, 
      apoptosis, migration, invasion, and epithelial-to-mesenchymal transition (EMT), 
      in the human thyroid cancer cell lines BCPAP and TPC-1. METHODS: BCPAP and TPC-1 
      cells were cultivated in Dulbecco's modified Eagle's medium, and the 
      non-tumor-derived cell line Nthy-ORI was grown in RPMI. Cells were treated or not 
      with AICAR for different periods of time. The cell growth rate, cell cycle phase, 
      apoptosis, cell migration, and invasion were analyzed using transwell inserts, 
      and EMT was quantified by the expression of mesenchymal and epithelial markers. 
      RESULTS: AMPK is activated in thyroid cancer cell lines, and AICAR treatment 
      further increased AMPK phosphorylation. After 48 hours of AICAR treatment, the 
      percentage of cells in the G2/M phase decreased, and a G0/G1-phase arrest was 
      induced in both cell lines. AMPK activation effectively induced apoptosis in the 
      BCPAP and TPC-1 cancer cell lines, while no apoptosis induction was observed in 
      Nthy-ORI cells. AICAR also reduced the migration of Nthy-ORI and BCPAP cells by 
      30% and approximately 60% in TPC-1 cells. AICAR had no effect on cell invasion in 
      Nthy-ORI and TPC-1 cells, but a significant reduction of cell invasion was 
      observed in BCPAP cells. AICAR induced a significant reduction of N-cadherin and 
      no changes in the expression of vimentin or TCF/Zeb1 protein in BCPAP cells. No 
      differences in the expression of EMT markers were found in the AICAR-treated 
      Nthy-ORI cells. A remarkable reduction of vimentin, TCF/Zeb1, and N-cadherin 
      protein expression was detected in the TPC-1 cells. CONCLUSIONS: Increased 
      activation of AMPK in PTC cell lines leads to a strong antitumor response, as 
      measured by the inhibition of cell proliferation, cell migration, and induction 
      of cell death. AMPK activation also reverses EMT in TPC-1 cells.
FAU - Cazarin, Juliana M
AU  - Cazarin JM
AD  - Laboratorio de Fisiologia Endocrina, Instituto de Biofisica Carlos Chagas Filho, 
      Universidade Federal do Rio de Janeiro , Rio de Janeiro, Brazil .
FAU - Coelho, Raquel G
AU  - Coelho RG
AD  - Laboratorio de Fisiologia Endocrina, Instituto de Biofisica Carlos Chagas Filho, 
      Universidade Federal do Rio de Janeiro , Rio de Janeiro, Brazil .
FAU - Hecht, Fabio
AU  - Hecht F
AD  - Laboratorio de Fisiologia Endocrina, Instituto de Biofisica Carlos Chagas Filho, 
      Universidade Federal do Rio de Janeiro , Rio de Janeiro, Brazil .
FAU - Andrade, Bruno M
AU  - Andrade BM
AD  - Laboratorio de Fisiologia Endocrina, Instituto de Biofisica Carlos Chagas Filho, 
      Universidade Federal do Rio de Janeiro , Rio de Janeiro, Brazil .
FAU - Carvalho, Denise P
AU  - Carvalho DP
AD  - Laboratorio de Fisiologia Endocrina, Instituto de Biofisica Carlos Chagas Filho, 
      Universidade Federal do Rio de Janeiro , Rio de Janeiro, Brazil .
LA  - eng
PT  - Journal Article
DEP - 20160603
PL  - United States
TA  - Thyroid
JT  - Thyroid : official journal of the American Thyroid Association
JID - 9104317
RN  - 0 (Ribonucleotides)
RN  - 360-97-4 (Aminoimidazole Carboxamide)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - F0X88YW0YK (AICA ribonucleotide)
SB  - IM
MH  - AMP-Activated Protein Kinases/*drug effects/metabolism
MH  - Aminoimidazole Carboxamide/*analogs & derivatives/pharmacology
MH  - Apoptosis/drug effects
MH  - Carcinoma, Papillary/*metabolism/pathology
MH  - Cell Cycle Checkpoints/*drug effects
MH  - Cell Line, Tumor
MH  - Cell Movement/*drug effects
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Epithelial-Mesenchymal Transition/*drug effects
MH  - G1 Phase Cell Cycle Checkpoints/drug effects
MH  - G2 Phase Cell Cycle Checkpoints/drug effects
MH  - Humans
MH  - Neoplasm Invasiveness
MH  - Ribonucleotides/*pharmacology
MH  - Thyroid Cancer, Papillary
MH  - Thyroid Neoplasms/*metabolism/pathology
EDAT- 2016/04/29 06:00
MHDA- 2018/02/07 06:00
CRDT- 2016/04/29 06:00
PHST- 2016/04/29 06:00 [entrez]
PHST- 2016/04/29 06:00 [pubmed]
PHST- 2018/02/07 06:00 [medline]
AID - 10.1089/thy.2015.0440 [doi]
PST - ppublish
SO  - Thyroid. 2016 Jul;26(7):933-42. doi: 10.1089/thy.2015.0440. Epub 2016 Jun 3.