Please use this identifier to cite or link to this item: https://doi.org/10.18632/oncotarget.23265
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dc.titleGRAM domain-containing protein 1B (GRAMD1B), a novel component of the JAK/STAT signaling pathway, functions in gastric carcinogenesis
dc.contributor.authorKhanna, P
dc.contributor.authorChua, P.J
dc.contributor.authorWong, B.S.E
dc.contributor.authorYin, C
dc.contributor.authorThike, A.A
dc.contributor.authorWan, W.K
dc.contributor.authorTan, P.H
dc.contributor.authorBaeg, G.H
dc.date.accessioned2020-09-01T00:56:46Z
dc.date.available2020-09-01T00:56:46Z
dc.date.issued2017
dc.identifier.citationKhanna, 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
dc.identifier.issn19492553
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/173797
dc.description.abstractDysregulated 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.
dc.sourceUnpaywall 20200831
dc.subjectcell protein
dc.subjectcomplementary DNA
dc.subjectcytokine
dc.subjectepidermal growth factor receptor
dc.subjectGRAM domain containing protein 1B
dc.subjectJanus kinase
dc.subjectmessenger RNA
dc.subjectnicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase inhibitor
dc.subjectprotein bcl xl
dc.subjectprotein mcl 1
dc.subjectSTAT protein
dc.subjectSTAT3 protein
dc.subjectsuppressor of cytokine signaling 2
dc.subjectsurvivin
dc.subjectunclassified drug
dc.subjectUnpaired protein
dc.subjectaged
dc.subjectArticle
dc.subjectbinding site
dc.subjectcancer classification
dc.subjectcancer grading
dc.subjectcancer patient
dc.subjectcell cycle arrest
dc.subjectcell cycle G1 phase
dc.subjectcell survival
dc.subjectcontrolled study
dc.subjectDrosophila
dc.subjectfeedback system
dc.subjectfemale
dc.subjectgastric adenocarcinoma cell line
dc.subjectgastric mucinous adenocarcinoma cell line
dc.subjectgastric signet ring cell adenocarcinoma cell line
dc.subjectgastric tubular adenocarcinoma cell line
dc.subjectgene expression
dc.subjecthuman
dc.subjecthuman cell
dc.subjecthuman tissue
dc.subjectimmunohistochemistry
dc.subjectmajor clinical study
dc.subjectmale
dc.subjectprotein cleavage
dc.subjectprotein domain
dc.subjectprotein expression
dc.subjectprotein function
dc.subjectprotein localization
dc.subjectprotein phosphorylation
dc.subjectprotein protein interaction
dc.subjectquantitative analysis
dc.subjectreal time polymerase chain reaction
dc.subjectsignal transduction
dc.subjectsignet ring carcinoma
dc.subjectstomach cancer
dc.subjectstomach carcinogenesis
dc.subjecttandem repeat
dc.subjecttissue microarray
dc.subjectupregulation
dc.typeArticle
dc.contributor.departmentDEPT OF ANATOMY
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.description.doi10.18632/oncotarget.23265
dc.description.sourcetitleOncotarget
dc.description.volume8
dc.description.issue70
dc.description.page115370-115383
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