PMID- 19779850
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20150203
LR  - 20211020
IS  - 1875-2284 (Electronic)
IS  - 1875-2292 (Print)
IS  - 1875-2284 (Linking)
VI  - 2
IP  - 1
DP  - 2009 Dec
TI  - The NF-kappaB/AKT-dependent Induction of Wnt Signaling in Colon Cancer Cells by 
      Macrophages and IL-1beta.
PG  - 69-80
LID - 10.1007/s12307-009-0030-y [doi]
AB  - Progression of colon cancer from microadenoma to macroscopic tumors is coupled to 
      augmentation of canonical Wnt signaling. We recently reported that tumor 
      associated macrophages, through interleukin 1beta (IL-1beta) dependent phosphorylation 
      of GSK3beta, promote Wnt signaling in colon cancer cells, demonstrating that 
      proinflammatory cytokines can enhance TCF4/beta-catenin transcriptional activity in 
      tumor cells. Here we investigated the pathway whereby IL-1beta inactivates GSK3beta and 
      promotes Wnt signaling in colon cancer cells. We showed that normal human 
      monocytes, THP1 macrophages and IL-1 failed to induce Wnt signaling in tumor 
      cells expressing dominant negative IkappaB (dnIkappaB), demonstrating that macrophages 
      and IL-1 activate Wnt signaling in a NF-kappaB-dependent manner. NF-kappaB activity was 
      required for macrophages and IL-1 to activate PDK1 and AKT in tumor cells and 
      thereby inhibit GSK3beta activity. Consistently, dominant negative AKT (dnAKT), or 
      pharmacological inhibition of AKT in tumor cells, prevented macrophage/IL-1 
      mediated phosphorylation of GSK3beta, activation of Wnt signaling, and induction of 
      c-jun and c-myc, confirming that macrophages and IL-1 promote Wnt signaling in an 
      AKT dependent manner. Finally, we showed IL-1 and macrophages failed to promote 
      growth of colon cancer cells with impaired NF-kappaB or AKT signaling, confirming the 
      requirement for NF-kappaB and AKT activation for the protumorigenic activity of tumor 
      associated macrophages. Thus, we showed that IL-1 and tumor associated 
      macrophages activate NF-kappaB-dependent PDK1/AKT signaling in tumor cells, and 
      thereby inactivate GSK3beta, enhance Wnt signaling and promote growth of colon 
      cancer cells, establishing a novel molecular link between inflammation and tumor 
      growth.
FAU - Kaler, Pawan
AU  - Kaler P
AD  - Albert Einstein Cancer Center, Department of Oncology, Montefiore Medical Center, 
      111 E 210 street, Bronx, NY 10467 USA.
FAU - Godasi, Bramara N
AU  - Godasi BN
AD  - Albert Einstein Cancer Center, Department of Oncology, Montefiore Medical Center, 
      111 E 210 street, Bronx, NY 10467 USA.
FAU - Augenlicht, Leonard
AU  - Augenlicht L
AD  - Albert Einstein Cancer Center, Department of Oncology, Montefiore Medical Center, 
      111 E 210 street, Bronx, NY 10467 USA.
FAU - Klampfer, Lidija
AU  - Klampfer L
AD  - Albert Einstein Cancer Center, Department of Oncology, Montefiore Medical Center, 
      111 E 210 street, Bronx, NY 10467 USA.
LA  - eng
GR  - R01 CA111361/CA/NCI NIH HHS/United States
GR  - U54 CA100926/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20090925
PL  - Netherlands
TA  - Cancer Microenviron
JT  - Cancer microenvironment : official journal of the International Cancer 
      Microenvironment Society
JID - 101322634
PMC - PMC2787930
OTO - NOTNLM
OT  - Colon cancer
OT  - Interleukin 1
OT  - Macrophages
OT  - NF kappaB signaling
OT  - Wnt signaling
EDAT- 2009/09/26 06:00
MHDA- 2009/09/26 06:01
PMCR- 2009/09/25
CRDT- 2009/09/26 06:00
PHST- 2009/06/17 00:00 [received]
PHST- 2009/08/18 00:00 [accepted]
PHST- 2009/09/26 06:00 [entrez]
PHST- 2009/09/26 06:00 [pubmed]
PHST- 2009/09/26 06:01 [medline]
PHST- 2009/09/25 00:00 [pmc-release]
AID - 30 [pii]
AID - 10.1007/s12307-009-0030-y [doi]
PST - epublish
SO  - Cancer Microenviron. 2009 Sep 25;2(1):69-80. doi: 10.1007/s12307-009-0030-y. 
      eCollection 2009 Dec.