PMID- 20627081
OWN - NLM
STAT- MEDLINE
DCOM- 20100825
LR  - 20211020
IS  - 1878-1551 (Electronic)
IS  - 1534-5807 (Print)
IS  - 1534-5807 (Linking)
VI  - 18
IP  - 6
DP  - 2010 Jun 15
TI  - Oncogenic Ras diverts a host TNF tumor suppressor activity into tumor promoter.
PG  - 999-1011
LID - 10.1016/j.devcel.2010.05.014 [doi]
AB  - The roles of inflammatory cytokines and the immune response in cancer remain 
      paradoxical. In the case of tumor necrosis factor (TNF), there is undisputed 
      evidence indicating both protumor and antitumor activities. Recent work in 
      Drosophila indicated that a TNF-dependent mechanism eliminates cells deficient 
      for the polarity tumor suppressors dlg or scrib. In this study, however, we show 
      that in tumors deficient for scrib that also expressed the Ras oncoprotein, the 
      TNF signal was diverted into a protumor signal that enhanced tumor growth through 
      larval arrest and stimulated invasive migration. In this case, TNF promoted 
      malignancy and was detrimental to host survival. TNF was expressed at high levels 
      by tumor-associated hemocytes recruited from the circulation. The expression of 
      TNF by hemocytes was both necessary and sufficient to trigger TNF signaling in 
      tumor cells. Our evidence suggests that tumors can evolve into malignancy through 
      oncogenic Ras activation and the hijacking of TNF signaling.
CI  - Copyright 2010 Elsevier Inc. All rights reserved.
FAU - Cordero, Julia B
AU  - Cordero JB
AD  - Beatson Institute for Cancer Research, Cancer Research UK, Garscube Estate, 
      Switchback Road, Bearsden, Glasgow G61 1BD, UK.
FAU - Macagno, Juan P
AU  - Macagno JP
FAU - Stefanatos, Rhoda K
AU  - Stefanatos RK
FAU - Strathdee, Karen E
AU  - Strathdee KE
FAU - Cagan, Ross L
AU  - Cagan RL
FAU - Vidal, Marcos
AU  - Vidal M
LA  - eng
GR  - R01 CA109730/CA/NCI NIH HHS/United States
GR  - R01 CA084309/CA/NCI NIH HHS/United States
GR  - R01CA109730/CA/NCI NIH HHS/United States
GR  - R01 CA109730-09/CA/NCI NIH HHS/United States
GR  - R01 CA084309-04/CA/NCI NIH HHS/United States
GR  - CRUK_/Cancer Research UK/United Kingdom
GR  - R01CA084309/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Dev Cell
JT  - Developmental cell
JID - 101120028
RN  - 0 (Carcinogens)
RN  - 0 (Drosophila Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Scrib protein, Drosophila)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
CIN - Future Oncol. 2010 Dec;6(12):1833-6. PMID: 21142857
MH  - Animals
MH  - Carcinogens/*metabolism
MH  - Cell Transformation, Neoplastic/genetics/immunology/metabolism
MH  - Drosophila Proteins/genetics/metabolism
MH  - Drosophila melanogaster
MH  - Gene Expression Regulation, Neoplastic/immunology
MH  - Hemocytes/cytology/immunology/metabolism
MH  - Membrane Proteins
MH  - Neoplasm Invasiveness/genetics/immunology
MH  - Neoplasms/genetics/*metabolism
MH  - Oncogenes/*physiology
MH  - Signal Transduction/physiology
MH  - Tumor Necrosis Factor-alpha/genetics/*metabolism
MH  - Tumor Suppressor Proteins/genetics/*metabolism
MH  - ras Proteins/genetics/*metabolism
PMC - PMC3175220
MID - NIHMS322775
EDAT- 2010/07/16 06:00
MHDA- 2010/08/26 06:00
PMCR- 2011/09/17
CRDT- 2010/07/15 06:00
PHST- 2009/11/05 00:00 [received]
PHST- 2010/03/15 00:00 [revised]
PHST- 2010/04/07 00:00 [accepted]
PHST- 2010/07/15 06:00 [entrez]
PHST- 2010/07/16 06:00 [pubmed]
PHST- 2010/08/26 06:00 [medline]
PHST- 2011/09/17 00:00 [pmc-release]
AID - S1534-5807(10)00250-9 [pii]
AID - 10.1016/j.devcel.2010.05.014 [doi]
PST - ppublish
SO  - Dev Cell. 2010 Jun 15;18(6):999-1011. doi: 10.1016/j.devcel.2010.05.014.