PMID- 29048643
OWN - NLM
STAT- MEDLINE
DCOM- 20180702
LR  - 20201209
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Linking)
VI  - 38
IP  - 5
DP  - 2017 Nov
TI  - Novel transduction of nutrient stress to Notch pathway by RasGRP3 promotes 
      malignant aggressiveness in human esophageal squamous cell carcinoma.
PG  - 2975-2984
LID - 10.3892/or.2017.5996 [doi]
AB  - In the process of enlarging of tumors, the dissolving tissue structures and 
      remodeling endothelial cells for restoring gas exchange and nutritional support, 
      further facilitate tumor cell invasion and metastasis. Activation of Ras plays a 
      critical role in the development of esophageal squamous cell carcinoma (ESCC), 
      but the underlying mechanisms remain poorly understood. We therefore investigated 
      whether Ras guanyl-releasing protein 3 (RasGRP3), a Ras activator, could promote 
      metastasis by inducing vascular regeneration and further epithelial-mesenchymal 
      transition under nutrient stress (NS). In the present study, we explored that the 
      accumulation of RasGRP3 regulated vascular endothelial growth factor-A 
      production, co-stimulated Notch pathway with high expression of Notch 
      intracellular domain (NICD) and Hes1. Moreover, ESCC cells under NS increased the 
      expression of vimentin, Snail, Slug and MMP9 proteins; while inhibition of Notch 
      activation by DAPT (a gamma-secretase inhibitor) or RasGRP3-targeted RNA interference 
      prevented from the effect. In conclusion, these findings provide a new insight 
      into the upregulation of RasGRP3 involved in Notch pathway activation in the 
      development of ESCC, especially under nutrient deprivation.
FAU - Hu, Ge
AU  - Hu G
AD  - Institute of Oncology, The Affiliated Hospital of Jiangsu University, Zhenjiang, 
      Jiangsu 212001, P.R. China.
FAU - Zhou, Yuepeng
AU  - Zhou Y
AD  - Institute of Oncology, The Affiliated Hospital of Jiangsu University, Zhenjiang, 
      Jiangsu 212001, P.R. China.
FAU - Zhu, Yu
AU  - Zhu Y
AD  - Institute of Oncology, The Affiliated Hospital of Jiangsu University, Zhenjiang, 
      Jiangsu 212001, P.R. China.
FAU - Zhou, Ling
AU  - Zhou L
AD  - Institute of Oncology, The Affiliated Hospital of Jiangsu University, Zhenjiang, 
      Jiangsu 212001, P.R. China.
FAU - Ling, Rui
AU  - Ling R
AD  - Institute of Oncology, The Affiliated Hospital of Jiangsu University, Zhenjiang, 
      Jiangsu 212001, P.R. China.
FAU - Wu, Dan
AU  - Wu D
AD  - Institute of Oncology, The Affiliated Hospital of Jiangsu University, Zhenjiang, 
      Jiangsu 212001, P.R. China.
FAU - Mi, Lei
AU  - Mi L
AD  - Institute of Oncology, The Affiliated Hospital of Jiangsu University, Zhenjiang, 
      Jiangsu 212001, P.R. China.
FAU - Wang, Xuefeng
AU  - Wang X
AD  - Central Laboratory, The Affiliated Hospital of Jiangsu University, Zhenjiang, 
      Jiangsu 212001, P.R. China.
FAU - Dai, Dongfang
AU  - Dai D
AD  - Institute of Oncology, The Affiliated Hospital of Jiangsu University, Zhenjiang, 
      Jiangsu 212001, P.R. China.
FAU - Mao, Chaoming
AU  - Mao C
AD  - Institute of Oncology, The Affiliated Hospital of Jiangsu University, Zhenjiang, 
      Jiangsu 212001, P.R. China.
FAU - Chen, Deyu
AU  - Chen D
AD  - Institute of Oncology, The Affiliated Hospital of Jiangsu University, Zhenjiang, 
      Jiangsu 212001, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20170925
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (Guanine Nucleotide Exchange Factors)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (RASGRP3 protein, human)
RN  - 0 (Receptors, Notch)
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (ras Guanine Nucleotide Exchange Factors)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Carcinoma, Squamous Cell/*genetics/metabolism/pathology
MH  - Cell Line, Tumor
MH  - Cell Movement/genetics
MH  - Epithelial-Mesenchymal Transition/*genetics
MH  - Esophageal Neoplasms/*genetics/metabolism/pathology
MH  - Esophageal Squamous Cell Carcinoma
MH  - Female
MH  - Food/adverse effects
MH  - Gene Expression Regulation, Neoplastic/genetics
MH  - Guanine Nucleotide Exchange Factors/*genetics
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Invasiveness/genetics
MH  - Neoplasm Metastasis
MH  - Neoplasm Proteins/genetics
MH  - Receptors, Notch/*genetics
MH  - Signal Transduction/genetics
MH  - Vascular Endothelial Growth Factor A
MH  - ras Guanine Nucleotide Exchange Factors
EDAT- 2017/10/20 06:00
MHDA- 2018/07/03 06:00
CRDT- 2017/10/20 06:00
PHST- 2017/04/06 00:00 [received]
PHST- 2017/08/28 00:00 [accepted]
PHST- 2017/10/20 06:00 [pubmed]
PHST- 2018/07/03 06:00 [medline]
PHST- 2017/10/20 06:00 [entrez]
AID - 10.3892/or.2017.5996 [doi]
PST - ppublish
SO  - Oncol Rep. 2017 Nov;38(5):2975-2984. doi: 10.3892/or.2017.5996. Epub 2017 Sep 25.