PMID- 24309932
OWN - NLM
STAT- MEDLINE
DCOM- 20140612
LR  - 20211105
IS  - 2041-4889 (Electronic)
VI  - 4
IP  - 12
DP  - 2013 Dec 5
TI  - Cancer-derived immunoglobulin G promotes tumor cell growth and proliferation 
      through inducing production of reactive oxygen species.
PG  - e945
LID - 10.1038/cddis.2013.474 [doi]
AB  - Cancer cells have been found to express immunoglobulin G (IgG), but the exact 
      functions and underlying mechanisms of cancer-derived IgG remain elusive. In this 
      study, we first confirmed that downregulation of IgG restrained the growth and 
      proliferation of cancer cells in vitro and in vivo. To elucidate its mechanism, 
      we carried out a co-immunoprecipitation assay in HeLa cells and identified 27 
      potential IgG-interacting proteins. Among them, receptor of activated protein 
      kinase C 1 (RACK1), ras-related nuclear protein (RAN) and peroxiredoxin 1 (PRDX1) 
      are closely related to cell growth and oxidative stress, which prompted us to 
      investigate the mechanism of action of IgG in the above phenomena. Upon 
      confirmation of the interactions between IgG and the three proteins, further 
      experiments revealed that downregulation of cancer-derived IgG lowered levels of 
      intracellular reactive oxygen species (ROS) by enhancing cellular total 
      antioxidant capacity. In addition, a few ROS scavengers, including catalase 
      (CAT), dimethylsulfoxide (DMSO), n-acetylcysteine (NAC) and superoxide dismutase 
      (SOD), further inhibited the growth of IgG-deficient cancer cells through 
      suppressing mitogen-activated protein kinase/extracellular-regulated kinase 
      (MAPK/ERK) signaling pathway induced by a low level of intracellular ROS, whereas 
      exogenous hydrogen peroxide (H2O2) at low concentration promoted their survival 
      via increasing intracellular ROS levels. Similar results were obtained in an 
      animal model and human tissues. Taken together, our results demonstrate that 
      cancer-derived IgG can enhance the growth and proliferation of cancer cells via 
      inducing the production of ROS at low level. These findings provide new clues for 
      understanding tumor proliferation and designing cancer therapy.
FAU - Wang, J
AU  - Wang J
AD  - Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, 
      Department of Pathology, Shantou University Medical College, Shantou, China.
FAU - Lin, D
AU  - Lin D
FAU - Peng, H
AU  - Peng H
FAU - Huang, Y
AU  - Huang Y
FAU - Huang, J
AU  - Huang J
FAU - Gu, J
AU  - Gu J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131205
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (Antioxidants)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Reactive Oxygen Species)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 1.11.1.15 (PRDX1 protein, human)
RN  - EC 1.11.1.15 (Peroxiredoxins)
RN  - EC 3.6.5.2 (ran GTP-Binding Protein)
SB  - IM
MH  - Antioxidants/metabolism
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Cytoplasm/metabolism
MH  - HeLa Cells
MH  - Humans
MH  - Hydrogen Peroxide/metabolism/pharmacology
MH  - Immunoglobulin G/*metabolism
MH  - Immunoprecipitation
MH  - Peroxiredoxins/metabolism
MH  - Protein Binding
MH  - Reactive Oxygen Species/*metabolism
MH  - ran GTP-Binding Protein/metabolism
PMC - PMC3877547
EDAT- 2013/12/07 06:00
MHDA- 2014/06/13 06:00
PMCR- 2013/12/01
CRDT- 2013/12/07 06:00
PHST- 2013/09/18 00:00 [received]
PHST- 2013/10/25 00:00 [revised]
PHST- 2013/10/29 00:00 [accepted]
PHST- 2013/12/07 06:00 [entrez]
PHST- 2013/12/07 06:00 [pubmed]
PHST- 2014/06/13 06:00 [medline]
PHST- 2013/12/01 00:00 [pmc-release]
AID - cddis2013474 [pii]
AID - 10.1038/cddis.2013.474 [doi]
PST - epublish
SO  - Cell Death Dis. 2013 Dec 5;4(12):e945. doi: 10.1038/cddis.2013.474.