PMID- 28881576
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20170925
LR  - 20181113
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 8
IP  - 31
DP  - 2017 Aug 1
TI  - Inhibition of PI3K/Akt/mTOR signaling in PI3KR2-overexpressing colon cancer stem 
      cells reduces tumor growth due to apoptosis.
PG  - 50476-50488
LID - 10.18632/oncotarget.9919 [doi]
AB  - In sporadic colon cancer, colon cancer stem cells (CCSCs) initiate tumorigenesis 
      and may contribute to late disease recurrences and metastases. We previously 
      showed that aldehyde dehydrogenase (ALDH) activity (as indicated by the 
      ALDEFLUOR((R)) assay) is an effective marker for highly enriching CCSCs for further 
      evaluation. Here, we used comparative transcriptome and proteome approaches to 
      identify signaling pathways overrepresented in the CCSC population. We found 
      overexpression of several components of the phosphoinositide 3-kinase 
      (PI3K)/Akt/mechanistic target of rapamycin (mTOR) signaling pathway, including 
      PI3KR2, a regulatory subunit of PI3K. LY294002, a PI3K inhibitor, defined the 
      contribution of the PI3K/Akt/mTOR signaling pathway in CCSCs. LY294002-treated 
      CCSCs showed decreases in proliferation, sphere formation and self-renewal, in 
      phosphorylation-dependent activation of Akt, and in expression of cyclin D1. 
      Inhibition of PI3K in vivo reduced tumorigenicity, increased detection of cleaved 
      caspase 3, an indicator of apoptosis, and elevated expression of the inflammatory 
      chemokine, CXCL8. Collectively, these results indicate that PI3K/Akt/mTOR 
      signaling controls CCSC proliferation and CCSC survival, and suggests that it 
      would be useful to develop therapeutic agents that target this signaling pathway.
FAU - Chen, Sugong
AU  - Chen S
AD  - Department of Surgery, University of Florida, Gainesville, Florida 32610, USA.
FAU - Fisher, Robert C
AU  - Fisher RC
AD  - Department of Surgery, University of Florida, Gainesville, Florida 32610, USA.
AD  - Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic 
      Lerner Research Institute, Cleveland, Ohio 44195, USA.
FAU - Signs, Steven
AU  - Signs S
AD  - Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic 
      Lerner Research Institute, Cleveland, Ohio 44195, USA.
FAU - Molina, L Alex
AU  - Molina LA
AD  - Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic 
      Lerner Research Institute, Cleveland, Ohio 44195, USA.
FAU - Shenoy, Anitha K
AU  - Shenoy AK
AD  - Department of Molecular Genetics and Microbiology, University of Florida, 
      Gainesville, Florida 32610, USA.
FAU - Lopez, Maria-Cecilia
AU  - Lopez MC
AD  - Department of Molecular Genetics and Microbiology, University of Florida, 
      Gainesville, Florida 32610, USA.
FAU - Baker, Henry V
AU  - Baker HV
AD  - Department of Molecular Genetics and Microbiology, University of Florida, 
      Gainesville, Florida 32610, USA.
FAU - Koomen, John M
AU  - Koomen JM
AD  - Molecular Oncology and Proteomics, SRB3, H. Lee Moffitt Cancer Center and 
      Research Institute, Tampa, Florida 33612, USA.
FAU - Chen, Yi
AU  - Chen Y
AD  - Molecular Oncology and Proteomics, SRB3, H. Lee Moffitt Cancer Center and 
      Research Institute, Tampa, Florida 33612, USA.
FAU - Gittleman, Haley
AU  - Gittleman H
AD  - Bioinformatics, Case Comprehensive Cancer Center, Cleveland, Ohio 44106, USA.
FAU - Barnholtz-Sloan, Jill
AU  - Barnholtz-Sloan J
AD  - Bioinformatics, Case Comprehensive Cancer Center, Cleveland, Ohio 44106, USA.
FAU - Berg, Annamarie
AU  - Berg A
AD  - Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic 
      Lerner Research Institute, Cleveland, Ohio 44195, USA.
FAU - Appelman, Henry D
AU  - Appelman HD
AD  - Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.
FAU - Huang, Emina H
AU  - Huang EH
AD  - Department of Surgery, University of Florida, Gainesville, Florida 32610, USA.
AD  - Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic 
      Lerner Research Institute, Cleveland, Ohio 44195, USA.
LA  - eng
GR  - U54 GM062119/GM/NIGMS NIH HHS/United States
GR  - R01 CA157663/CA/NCI NIH HHS/United States
GR  - R01 CA142808/CA/NCI NIH HHS/United States
GR  - P30 CA043703/CA/NCI NIH HHS/United States
GR  - P30 CA076292/CA/NCI NIH HHS/United States
GR  - T32 CA106493/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20160608
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
PMC - PMC5584153
OTO - NOTNLM
OT  - ALDEFLUOR
OT  - PI3K/Akt/mTOR signaling
OT  - apoptosis
OT  - colon cancer stem cells
OT  - tumorigenesis
COIS- CONFLICTS OF INTEREST The authors declare no conflicts of interest.
EDAT- 2016/06/08 00:00
MHDA- 2016/06/08 00:01
PMCR- 2017/08/01
CRDT- 2017/09/09 06:00
PHST- 2016/02/05 00:00 [received]
PHST- 2016/05/19 00:00 [accepted]
PHST- 2017/09/09 06:00 [entrez]
PHST- 2016/06/08 00:00 [pubmed]
PHST- 2016/06/08 00:01 [medline]
PHST- 2017/08/01 00:00 [pmc-release]
AID - 9919 [pii]
AID - 10.18632/oncotarget.9919 [doi]
PST - epublish
SO  - Oncotarget. 2016 Jun 8;8(31):50476-50488. doi: 10.18632/oncotarget.9919. 
      eCollection 2017 Aug 1.