PMID- 25738361
OWN - NLM
STAT- MEDLINE
DCOM- 20160218
LR  - 20190108
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 6
IP  - 6
DP  - 2015 Feb 28
TI  - Cytoplasmic TRAF4 contributes to the activation of p70s6k signaling pathway in 
      breast cancer.
PG  - 4080-96
AB  - Tumor necrosis factor receptor associated factor 4 (TRAF4) is an important 
      adaptor protein that plays a significant role in several signaling pathways. By 
      studying the relationship between TRAF4 and 70 kDa ribosomal protein S6 kinase 
      (p70s6k) in vivo, we demonstrated that cytoplasmic TRAF4 was correlated with the 
      activation of p70s6k in breast cancer. Moreover, we found that cytoplasmic TRAF4 
      expression in breast cancer patients was significantly associated with a poor 
      prognosis. To determine the exact mechanism, we analyzed the interaction between 
      TRAF4 and p70s6k and identified the Zinc fingers domain of TRAF4 was responsible 
      for their interaction in MCF7 cells. Furthermore, we found that activation of 
      p70s6k/S6 signaling pathway by TRAF4 requires the mammalian target of rapamycin 
      (mTOR) activity; TRAF4 acted as a sensitizer. Tumor necrosis factor receptor 
      associated factor 2 (TRAF2), as a binding partner of TRAF4, could also promoted 
      activation of p70s6k signaling via upregulating cytoplasm expression of TRAF4 and 
      played a critical role in TNFa-induced activation of p70s6k/S6 pathway. Finally, 
      we demonstrated p70s6k/S6 signaling pathway played an important role in the 
      promoting function of TRAF4 on cell proliferation. In summary, our work suggests 
      a new direction for understanding the oncogenic function of TRAF4 in breast 
      cancer.
FAU - Ren, Hua-Yan
AU  - Ren HY
AD  - Department of Pathology, First Affiliated Hospital and College of Basic Medical 
      Sciences, China Medical University, Shenyang 110001, P.R. China.
FAU - Wang, Jian
AU  - Wang J
AD  - Department of Pathology, First Affiliated Hospital and College of Basic Medical 
      Sciences, China Medical University, Shenyang 110001, P.R. China.
FAU - Yang, Fan
AU  - Yang F
AD  - Department of Pathology, First Affiliated Hospital and College of Basic Medical 
      Sciences, China Medical University, Shenyang 110001, P.R. China.
FAU - Zhang, Xiao-Li
AU  - Zhang XL
AD  - Department of Pathology, First Affiliated Hospital and College of Basic Medical 
      Sciences, China Medical University, Shenyang 110001, P.R. China.
FAU - Wang, Ai-Lian
AU  - Wang AL
AD  - Department of Pathology, First Affiliated Hospital and College of Basic Medical 
      Sciences, China Medical University, Shenyang 110001, P.R. China.
FAU - Sun, Li-Li
AU  - Sun LL
AD  - Department of Pathology, First Affiliated Hospital and College of Basic Medical 
      Sciences, China Medical University, Shenyang 110001, P.R. China.
FAU - Diao, Ke-Xin
AU  - Diao KX
AD  - Department of Pathology, First Affiliated Hospital and College of Basic Medical 
      Sciences, China Medical University, Shenyang 110001, P.R. China.
FAU - Wang, En-Hua
AU  - Wang EH
AD  - Department of Pathology, First Affiliated Hospital and College of Basic Medical 
      Sciences, China Medical University, Shenyang 110001, P.R. China.
FAU - Mi, Xiao-Yi
AU  - Mi XY
AD  - Department of Pathology, First Affiliated Hospital and College of Basic Medical 
      Sciences, China Medical University, Shenyang 110001, P.R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (TNF Receptor-Associated Factor 4)
RN  - 0 (TRAF4 protein, human)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
SB  - IM
MH  - Breast Neoplasms/*metabolism/pathology
MH  - Cell Proliferation/physiology
MH  - Cytoplasm/metabolism
MH  - Female
MH  - Humans
MH  - MCF-7 Cells
MH  - Ribosomal Protein S6 Kinases, 70-kDa/*metabolism
MH  - Signal Transduction
MH  - TNF Receptor-Associated Factor 4/*metabolism
PMC - PMC4414174
EDAT- 2015/03/05 06:00
MHDA- 2016/02/19 06:00
PMCR- 2015/02/01
CRDT- 2015/03/05 06:00
PHST- 2014/08/20 00:00 [received]
PHST- 2014/12/18 00:00 [accepted]
PHST- 2015/03/05 06:00 [entrez]
PHST- 2015/03/05 06:00 [pubmed]
PHST- 2016/02/19 06:00 [medline]
PHST- 2015/02/01 00:00 [pmc-release]
AID - 2977 [pii]
AID - 10.18632/oncotarget.2977 [doi]
PST - ppublish
SO  - Oncotarget. 2015 Feb 28;6(6):4080-96. doi: 10.18632/oncotarget.2977.