Please use this identifier to cite or link to this item: https://doi.org/10.18632/oncotarget.23265
Title: GRAM domain-containing protein 1B (GRAMD1B), a novel component of the JAK/STAT signaling pathway, functions in gastric carcinogenesis
Authors: Khanna, P
Chua, P.J 
Wong, B.S.E 
Yin, C
Thike, A.A
Wan, W.K 
Tan, P.H 
Baeg, G.H 
Keywords: cell protein
complementary DNA
cytokine
epidermal growth factor receptor
GRAM domain containing protein 1B
Janus kinase
messenger RNA
nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase inhibitor
protein bcl xl
protein mcl 1
STAT protein
STAT3 protein
suppressor of cytokine signaling 2
survivin
unclassified drug
Unpaired protein
aged
Article
binding site
cancer classification
cancer grading
cancer patient
cell cycle arrest
cell cycle G1 phase
cell survival
controlled study
Drosophila
feedback system
female
gastric adenocarcinoma cell line
gastric mucinous adenocarcinoma cell line
gastric signet ring cell adenocarcinoma cell line
gastric tubular adenocarcinoma cell line
gene expression
human
human cell
human tissue
immunohistochemistry
major clinical study
male
protein cleavage
protein domain
protein expression
protein function
protein localization
protein phosphorylation
protein protein interaction
quantitative analysis
real time polymerase chain reaction
signal transduction
signet ring carcinoma
stomach cancer
stomach carcinogenesis
tandem repeat
tissue microarray
upregulation
Issue Date: 2017
Citation: Khanna, P, Chua, P.J, Wong, B.S.E, Yin, C, Thike, A.A, Wan, W.K, Tan, P.H, Baeg, G.H (2017). GRAM domain-containing protein 1B (GRAMD1B), a novel component of the JAK/STAT signaling pathway, functions in gastric carcinogenesis. Oncotarget 8 (70) : 115370-115383. ScholarBank@NUS Repository. https://doi.org/10.18632/oncotarget.23265
Abstract: Dysregulated JAK/STAT signaling has been implicated in the molecular pathogenesis of gastric cancer. However, downstream effectors of STAT signaling that facilitate gastric carcinogenesis remain to be explored. We previously identified the Drosophila ortholog of human GRAMD1B in our genome-wide RNAi screen to identify novel components of the JAK/STAT signaling pathway in Drosophila. Here, we examined the involvement of GRAMD1B in JAK/STAT-associated gastric carcinogenesis. We found that GRAMD1B expression is positively regulated by JAK/STAT signaling and GRAMD1B inhibition decreases STAT3 levels, suggesting the existence of a positive feedback loop. Consistently, GRAMD1B and JAK/STAT signaling acted synergistically to promote gastric cancer cell survival by upregulating the expression of the anti-apoptotic molecule Bcl-xL. Interestingly, our immunohistochemical analysis for GRAMD1B revealed a gradual loss of cytoplasmic staining but an increase in the nuclear accumulation of GRAMD1B, as gastric tissue becomes malignant. GRAMD1B expression levels were also found to be significantly associated with clinicopathological features of the gastric cancer patients, particularly the tumor grades and lymph node status. Moreover, GRAMD1B and pSTAT3 (Tyr705) showed a positive correlation in gastric tissues, thereby confirming the existence of a close link between these two signaling molecules in vivo. This new knowledge about JAK/STAT-GRAMD1B regulation deepens our understanding of JAK/STAT signaling in gastric carcinogenesis and provides a foundation for the development of novel biomarkers in gastric cancer. © Khanna et al.
Source Title: Oncotarget
URI: https://scholarbank.nus.edu.sg/handle/10635/173797
ISSN: 19492553
DOI: 10.18632/oncotarget.23265
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