PMID- 28562353
OWN - NLM
STAT- MEDLINE
DCOM- 20180504
LR  - 20191210
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 8
IP  - 26
DP  - 2017 Jun 27
TI  - IL-17RC is critically required to maintain baseline A20 production to repress JNK 
      isoform-dependent tumor-specific proliferation.
PG  - 43153-43168
LID - 10.18632/oncotarget.17820 [doi]
AB  - The IL-17/IL-17R axis has controversial roles in cancer, which may be explained 
      by tumor-specific results. Here, we describe a novel molecular mechanism 
      underlying IL-17RC-controlled tumor-specific proliferation. Triggered by IL-17RC 
      knockdown (KD), B16 melanoma and 4T1 carcinoma cells inversely altered 
      homeostatic tumor proliferation and tumor growth in vitro and in vivo. In 
      contrast to the existing dogma that IL-17RC-dependent signaling activates the JNK 
      pathway, IL-17RC KD in both tumor cell lines caused aberrant expression and 
      activation of different JNK isoforms along with markedly diminished levels of the 
      ubiquitin-editing enzyme A20. We demonstrated that differential up-regulation of 
      JNK1 and JNK2 in the two tumor cell lines was responsible for the reciprocal 
      regulation of c-Jun activity and tumor-specific proliferation. Furthermore, we 
      showed that A20 reconstitution of IL-17RCKD clones with expression of full-length 
      A20, but not a truncation-mutant, reversed aberrant JNK1/JNK2 activities and 
      tumor-specific proliferation. Collectively, our study reveals a critical role of 
      IL-17RC in maintaining baseline A20 production and a novel role of the 
      IL-17RC-A20 axis in controlling JNK isoform-dependent tumor-specific homeostatic 
      proliferation.
FAU - Yan, Chi
AU  - Yan C
AD  - Canadian Center for Vaccinology, Halifax, Nova Scotia, Canada.
AD  - Department of Microbiology and Immunology, Faculty of Medicine, Dalhousie 
      University, Halifax, Nova Scotia, Canada.
FAU - Lei, Yang
AU  - Lei Y
AD  - Canadian Center for Vaccinology, Halifax, Nova Scotia, Canada.
AD  - Department of Microbiology and Immunology, Faculty of Medicine, Dalhousie 
      University, Halifax, Nova Scotia, Canada.
FAU - Lin, Tong-Jun
AU  - Lin TJ
AD  - Department of Microbiology and Immunology, Faculty of Medicine, Dalhousie 
      University, Halifax, Nova Scotia, Canada.
AD  - Department of Pediatrics, Faculty of Medicine, Dalhousie University, Halifax, 
      Nova Scotia, Canada.
AD  - IWK Health Centre, Halifax, Nova Scotia, Canada.
FAU - Hoskin, David W
AU  - Hoskin DW
AD  - Department of Microbiology and Immunology, Faculty of Medicine, Dalhousie 
      University, Halifax, Nova Scotia, Canada.
AD  - Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada.
FAU - Ma, Averil
AU  - Ma A
AD  - Department of Medicine, University of California, San Francisco, California, USA.
FAU - Wang, Jun
AU  - Wang J
AD  - Canadian Center for Vaccinology, Halifax, Nova Scotia, Canada.
AD  - Department of Microbiology and Immunology, Faculty of Medicine, Dalhousie 
      University, Halifax, Nova Scotia, Canada.
AD  - Department of Pediatrics, Faculty of Medicine, Dalhousie University, Halifax, 
      Nova Scotia, Canada.
AD  - IWK Health Centre, Halifax, Nova Scotia, Canada.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (Il17ra protein, mouse)
RN  - 0 (Interleukin-17)
RN  - 0 (Isoenzymes)
RN  - 0 (Receptors, Interleukin-17)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 4)
RN  - EC 3.4.19.12 (Tumor Necrosis Factor alpha-Induced Protein 3)
RN  - EC 3.4.22.- (Tnfaip3 protein, mouse)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Cell Proliferation/physiology
MH  - Female
MH  - Interleukin-17/metabolism
MH  - Isoenzymes
MH  - MAP Kinase Kinase 4/antagonists & inhibitors/metabolism
MH  - Male
MH  - Mammary Neoplasms, Experimental/enzymology/genetics/*metabolism/pathology
MH  - Melanoma/*genetics/*metabolism
MH  - Melanoma, Experimental/enzymology/genetics/*metabolism/pathology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Receptors, Interleukin-17/genetics/*metabolism
MH  - Signal Transduction
MH  - Transcription Factors/metabolism
MH  - Transfection
MH  - Tumor Necrosis Factor alpha-Induced Protein 3/*biosynthesis/genetics
PMC - PMC5522135
OTO - NOTNLM
OT  - A20
OT  - B16 melanoma
OT  - IL-17 receptor C
OT  - JNK1
OT  - JNK2
COIS- CONFLICTS OF INTEREST The authors have declared that no conflicts of interest 
      exists.
EDAT- 2017/06/01 06:00
MHDA- 2018/05/05 06:00
PMCR- 2017/06/27
CRDT- 2017/06/01 06:00
PHST- 2017/02/04 00:00 [received]
PHST- 2017/04/17 00:00 [accepted]
PHST- 2017/06/01 06:00 [pubmed]
PHST- 2018/05/05 06:00 [medline]
PHST- 2017/06/01 06:00 [entrez]
PHST- 2017/06/27 00:00 [pmc-release]
AID - 17820 [pii]
AID - 10.18632/oncotarget.17820 [doi]
PST - ppublish
SO  - Oncotarget. 2017 Jun 27;8(26):43153-43168. doi: 10.18632/oncotarget.17820.