GRAM domain-containing protein 1B (GRAMD1B), a novel component of the JAK/STAT signaling pathway, functions in gastric carcinogenesis

Khanna, Puja; Chua, Pei Jou; Wong, Belinda Shu Ee; Yin, Changhong; Thike, Aye Aye; Wan, Wei Keat; Tan, Puay Hoon; Baeg, Gyeong Hun

doi:10.18632/oncotarget.23265

Cited by 15 publications

(22 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, a genome-wide association study in chronic lymphocytic leukemia patients revealed that single nucleotide polymorphism in Gramd1b is associated with increased risk of disease in a European population 21 . In gastric cancer, GRAMD1B regulates cell survival by upregulating expression of the anti-apoptotic molecule Bcl-xL 22 . In this study, JAK/STAT signaling was found to positively regulate GRAMD1B expression in the breast cancer MDA-MB-231 cells.…”

Section: Introductionmentioning

confidence: 99%

GRAMD1B regulates cell migration in breast cancer cells through JAK/STAT and Akt signaling

Khanna

Lee

Sereemaspun

et al. 2018

Sci Rep

Self Cite

View full text Add to dashboard Cite

Dysregulated JAK/STAT signaling has been implicated in breast cancer metastasis, which is associated with high relapse risks. However, mechanisms underlying JAK/STAT signaling-mediated breast tumorigenesis are poorly understood. Here, we showed that GRAMD1B expression is upregulated on IL-6 but downregulated upon treatment with the JAK2 inhibitor AG490 in the breast cancer MDA-MB-231 cells. Notably, Gramd1b knockdown caused morphological changes of the cells, characterized by the formation of membrane ruffling and protrusions, implicating its role in cell migration. Consistently, GRAMD1B inhibition significantly enhanced cell migration, with an increase in the levels of the Rho family of GTPases. We also found that Gramd1b knockdown-mediated pro-migratory phenotype is associated with JAK2/STAT3 and Akt activation, and that JAK2 or Akt inhibition efficiently suppresses the phenotype. Interestingly, AG490 dose-dependently increased p-Akt levels, and our epistasis analysis suggested that the effect of JAK/STAT inhibition on p-Akt is via the regulation of GRAMD1B expression. Taken together, our results suggest that GRAMD1B is a key signaling molecule that functions to inhibit cell migration in breast cancer by negating both JAK/STAT and Akt signaling, providing the foundation for its development as a novel biomarker in breast cancer.

show abstract

Section: Introductionmentioning

confidence: 99%

GRAMD1B regulates cell migration in breast cancer cells through JAK/STAT and Akt signaling

Khanna

Lee

Sereemaspun

et al. 2018

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…Constitutive activation of JAK/STAT signaling is well‐established in cancers. Aberrant JAK/STAT signaling also is crucial to the development of GC, in particular, aberrant STAT3 expression has been implicated in GA patients 35–37 . Huang et al found that oxymatrine exhibits the effects via regulation of JAK/STAT signaling pathway and exhibits antitumor activity in GC 38 .…”

Section: Discussionmentioning

confidence: 99%

Diagnostic and therapeutic potencies of miR‐18a‐5p in mixed‐type gastric adenocarcinoma

Wang

Zhang

Wang

et al. 2021

J of Cellular Biochemistry

View full text Add to dashboard Cite

Mixed‐type gastric adenocarcinoma (by Lauren Classification) has poor clinical outcomes with few targeted treatment options. The primary objective of this study was to find the prognostic factors, accurate treatment approaches, and effective postoperative adjuvant therapy strategies for patients with mixed‐type gastric adenocarcinoma (GA). A microRNA sequencing data set and the corresponding clinical parameters of patients with gastric cancer were obtained from The Cancer Genome Atlas. Differentially expressed microRNAs (DEMs) of diffuse‐ and intestinal‐type GA were, respectively, determined. Kaplan–Meier and log‐rank tests were subsequently carried out to evaluate the prognostic relevance of each DEM. To study the common factors between diffuse‐ and intestinal‐type GA, a pathway enrichment analysis was performed on the target genes of identified DEMs using the PANTHER database. After data preprocessing, we analyzed a total of 230 samples from 210 patients with GA. Eighty‐six DEMs in diffuse‐type GA samples and 59 DEMs in intestinal‐type GA samples were, respectively, identified (p 2.0). The Kaplan–Meier survival method further screened out six prognosis‐related DEMs for diffuse‐type GA and seven prognosis‐related DEMs for intestinal‐type GA (p < 0.05). MiR‐18a‐5p was found to be the only common prognosis‐related DEM between diffuse‐ and intestinal‐type GA. The common signaling pathways further revealed that target genes of miR‐18a‐5p are involved in mixed‐type GA progression. This study suggests that miR‐18a‐5p acts as a potential target for treatment, and common signal pathways provide a rich basis to seek reliable and effective molecular targets for the diagnosis, clinical treatment, and postoperative adjuvant therapy strategy of mixed‐type GA.

show abstract

“…SOCS2 can be activated through tyrosine phosphorylation and may act as a downstream factor of the JAK/STAT pathway, providing a negative feedback regulation to this signaling pathway (38). Indeed, the JAK/STAT signal pathway is often dysregulated in gastric cancer (39). The JAK/STAT signaling pathway participates in multiple cancerous cellular processes: apoptosis, proliferation, metastasis and inflammation (40)(41)(42)(43).…”

Section: Discussionmentioning

confidence: 99%

Knockdown of m6A methyltransferase METTL3 in gastric cancer cells results in suppression of cell proliferation

Jiang

Chen

et al. 2020

Oncol Lett

View full text Add to dashboard Cite

N6-methyladenosine (m6A) RNA modification regulates multiple biological functions. Methyltransferase like 3 (METTL3), one of the major N6-methyltransferases, is highly expressed in gastric cancer, but its potential role in disease is unclear. The current study knocked out METTL3 (METTL3-KO) in human gastric cancer AGS cells using CRISPR/Cas9. METTL3-KO AGS cells exhibited decreased m6A methylation levels. A significant inhibition of cell proliferation was observed in METTL3-KO AGS cells. Silencing METTL3 in AGS cells altered the expression profile of many effector molecules that were previously demonstrated to serve key roles in AGS cell proliferation, including the suppressor of cytokine signaling (SOCS) family of proteins. The results further demonstrated that SOCS2 upregulation in METTL3-KO AGS cells was associated with a decreased RNA decay rate. Furthermore, SOCS2 KO or SOCS2 overexpression caused a significant increase and decrease in AGS cell proliferation, respectively. The current data suggested that METTL3-KO in gastric cancer cells resulted in the suppression of cell proliferation by inducing SOCS2, suggesting a potential role of elevated METTL3 expression in gastric cancer progression.

show abstract

GRAM domain-containing protein 1B (GRAMD1B), a novel component of the JAK/STAT signaling pathway, functions in gastric carcinogenesis

Cited by 15 publications

References 54 publications

GRAMD1B regulates cell migration in breast cancer cells through JAK/STAT and Akt signaling

GRAMD1B regulates cell migration in breast cancer cells through JAK/STAT and Akt signaling

Diagnostic and therapeutic potencies of miR‐18a‐5p in mixed‐type gastric adenocarcinoma

Knockdown of m6A methyltransferase METTL3 in gastric cancer cells results in suppression of cell proliferation

Contact Info

Product

Resources

About