PMID- 30839135
OWN - NLM
STAT- MEDLINE
DCOM- 20200221
LR  - 20200221
IS  - 1095-8355 (Electronic)
IS  - 1065-6995 (Linking)
VI  - 43
IP  - 11
DP  - 2019 Nov
TI  - TNF-alpha mediated MEK-ERK signaling in invasion with putative network involving 
      NF-kappaB and STAT-6: a new perspective in glioma.
PG  - 1257-1266
LID - 10.1002/cbin.11125 [doi]
AB  - Glioblastoma is the most common malignant primary brain tumor with poor 
      prognosis. Invasion involves pro-inflammatory cytokines and major signaling hubs. 
      Tumor necrosis factor-alpha (TNF-alpha) acts as a master switch in establishing an 
      intricate link between inflammation and cancer. The present study attempted to 
      explore the possible implication of MAPK extracellular signaling-regulated kinase 
      kinase (MEK)-extracellular signaling-regulated kinase (ERK) signaling pathway and 
      expression of nuclear factor-kappaB (NF-kappaB), signal transducers and activators of 
      transcription-6 (STAT-6), ERK, and phosphorylated-ERK (p-ERK) signaling proteins 
      in TNF-alpha microenvironment. U0126 and PD98059 were used to inhibit the MEK-ERK1/2 
      pathway. TNF-alpha stimulation enhanced invasion in U87MG, U251MG and patient-derived 
      primary glioma cells, whereas cell viability was not altered. Matrix 
      metalloproteinase-2 (MMP-2) activity was increased only in U251MG glioma cells. 
      These data suggest that TNF-alpha microenvironment plays an important role in the 
      invasion of U251MG, U87MG, and patient-derived primary glioma cells, without any 
      cytotoxic effect. The MMP-2 activity is differentially regulated by TNF-alpha 
      stimulation in these cells. TNF-alpha stimulation upregulated the protein expression 
      of ERK-1, ERK-2 and also increased the level of p-ERK1/2. TNF-alpha stimulation 
      further upregulated the expression of NF-kappaB1, STAT-6 in tandem with Ras-MEK 
      signaling system in U87MG cells, which emphasized the possible involvement of 
      these signaling hubs in the glioma microenvironment. MEK-ERK inhibitors 
      significantly attenuated the invasion of U87MG cells mediated by the TNF-alpha 
      stimulation, probably through their inhibitory impact on p-ERK1/2 and ERK-2. This 
      study provides the possible rationale of invasion by glioma cells in a 
      TNF-alpha-induced pro-inflammatory milieu, which involves direct role of MEK-ERK 
      signaling, with possible implication of NF-kappaB and STAT-6.
CI  - (c) 2019 International Federation for Cell Biology.
FAU - Ramaswamy, Palaniswamy
AU  - Ramaswamy P
AD  - Department of Neurochemistry, National Institute of Mental Health and Neuro 
      Sciences (NIMHANS), Bengaluru, 560029, India.
FAU - Goswami, Kalyan
AU  - Goswami K
AD  - Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), 
      Raipur, 492099, India.
FAU - Dalavaikodihalli Nanjaiah, Nandakumar
AU  - Dalavaikodihalli Nanjaiah N
AD  - Department of Neurochemistry, National Institute of Mental Health and Neuro 
      Sciences (NIMHANS), Bengaluru, 560029, India.
FAU - Srinivas, Dwarakanath
AU  - Srinivas D
AD  - Department of Neurosurgery, National Institute of Mental Health and Neuro 
      Sciences (NIMHANS), Bengaluru, 560029, India.
FAU - Prasad, Chandrajit
AU  - Prasad C
AD  - Department of Neuroimaging and Intervention Radiology, National Institute of 
      Mental Health and Neuro Sciences (NIMHANS), Bengaluru, 560029, India.
LA  - eng
PT  - Journal Article
DEP - 20190716
PL  - England
TA  - Cell Biol Int
JT  - Cell biology international
JID - 9307129
RN  - 0 (NF-kappa B)
RN  - 0 (STAT6 Transcription Factor)
RN  - 0 (STAT6 protein, human)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinases)
SB  - IM
MH  - Brain Neoplasms/*metabolism
MH  - Cell Line, Tumor
MH  - Cell Movement
MH  - Extracellular Signal-Regulated MAP Kinases/*metabolism
MH  - Gliosarcoma/*metabolism
MH  - Humans
MH  - MAP Kinase Kinase Kinases/*metabolism
MH  - MAP Kinase Signaling System
MH  - NF-kappa B/metabolism
MH  - STAT6 Transcription Factor/metabolism
MH  - Signal Transduction
MH  - Tumor Microenvironment
MH  - Tumor Necrosis Factor-alpha/*physiology
OTO - NOTNLM
OT  - cytokine
OT  - glioblastoma
OT  - hub
OT  - inflammation
OT  - invasion
OT  - signaling
EDAT- 2019/03/07 06:00
MHDA- 2020/02/23 06:00
CRDT- 2019/03/07 06:00
PHST- 2019/01/03 00:00 [received]
PHST- 2019/03/02 00:00 [accepted]
PHST- 2019/03/07 06:00 [pubmed]
PHST- 2020/02/23 06:00 [medline]
PHST- 2019/03/07 06:00 [entrez]
AID - 10.1002/cbin.11125 [doi]
PST - ppublish
SO  - Cell Biol Int. 2019 Nov;43(11):1257-1266. doi: 10.1002/cbin.11125. Epub 2019 Jul 
      16.