The oncogenic JAG1 intracellular domain is a transcriptional cofactor that acts in concert with DDX17/SMAD3/TGIF2

Kim, Eun-Jung; Kim, Jung Yun; Kim, Sung-Ok; Hong, Na-Young; Choi, Sang‐Hun; Park, Min Gi; Jang, Jeong-Hwan; Ham, Seok Won; Seo, Sunyoung; Lee, Seon Yong; Lee, Kanghun; Jeong, Hyeon Ju; Kim, Sung Jin; Jeong, Soon-Ki; Min, Kyungim; Kim, Sung‐Chan; Jin, Xiong; Kim, Se Hoon; Kim, Sung-Hak; Kim, Hyunggee

doi:10.1016/j.celrep.2022.111626

Cited by 8 publications

(21 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our previous study, JAG1 was highly expressed in human glioma patients, and some tumor cells exhibited nuclear JAG1 expression [ 16 ]. A part of the JAG1 protein, JICD1, is found in the nuclear fraction and its formation is repressed by the γ-secretase inhibitor, DAPT [ 16 ]. JAG1 and JICD1 were highly expressed in LN229 than in U87MG cells (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

“…In tumors, JAG1 intracellular domain (JICD1) formation is enhanced by oncogenic signaling, including the interleukin-4 (IL-4)-phosphatidylinositol 3-kinase d (PI3Kd)/protein kinase B (AKT) or Kirsten rat sarcoma virus (KRAS)/extracellular signal-regulated kinase (ERK)/ADAM17 signal [ 14 , 15 ]. Furthermore, our previous study showed that JICD1 enhances tumorigenesis by forming a transcriptional complex with DEAD-box helicase 17 (DDX17)/SMAD family member 3 (SMAD3)/TGFβ-induced factor homeobox 2 (TGIF2) [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Jagged1 intracellular domain/SMAD3 complex transcriptionally regulates TWIST1 to drive glioma invasion

Kim,

Hong,

Park

et al. 2023

Cell Death Dis

Self Cite

View full text Add to dashboard Cite

Jagged1 (JAG1) is a Notch ligand that correlates with tumor progression. Not limited to its function as a ligand, JAG1 can be cleaved, and its intracellular domain translocates to the nucleus, where it functions as a transcriptional cofactor. Previously, we showed that JAG1 intracellular domain (JICD1) forms a protein complex with DDX17/SMAD3/TGIF2. However, the molecular mechanisms underlying JICD1-mediated tumor aggressiveness remains unclear. Here, we demonstrate that JICD1 enhances the invasive phenotypes of glioblastoma cells by transcriptionally activating epithelial-to-mesenchymal transition (EMT)-related genes, especially TWIST1. The inhibition of TWIST1 reduced JICD1-driven tumor aggressiveness. Although SMAD3 is an important component of transforming growth factor (TGF)-β signaling, the JICD1/SMAD3 transcriptional complex was shown to govern brain tumor invasion independent of TGF-β signaling. Moreover, JICD1-TWIST1-MMP2 and MMP9 axes were significantly correlated with clinical outcome of glioblastoma patients. Collectively, we identified the JICD1/SMAD3-TWIST1 axis as a novel inducer of invasive phenotypes in cancer cells.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Jagged1 intracellular domain/SMAD3 complex transcriptionally regulates TWIST1 to drive glioma invasion

Kim,

Hong,

Park

et al. 2023

Cell Death Dis

Self Cite

View full text Add to dashboard Cite

show abstract

“…12,13,[21][22][23][24][25][26] JAG1 upregulation has been associated with several types of cancer. 14,27 It is noteworthy that Alagille syndrome is associated with hepatocellular carcinoma risk, with 21 reported pediatric patients. [28][29][30] Furthermore, rare pediatric cases of Alagille syndrome with hepatoblastoma, hepatic adenomas, and giant hepatic regenerative nodules have also been described.…”

Section: E T T E R T O T H E E D I T O R a Rare Case Of Hepatoblastom...mentioning

confidence: 99%

“…14,34 The JAG1 intracellular domain, here found to be germline mutated, was reported to act as a transcriptional cofactor, establishing an oncogenic transcriptional complex that promotes cancer cell stemness and aggressiveness. 27 Considering the location of the germline mutation in the last exon, the mRNA could escape from the nonsense-mediated RNA decay, resulting in a truncated protein with an oncogenic signal that could contribute to hepatoblastoma development.…”

Section: E T T E R T O T H E E D I T O R a Rare Case Of Hepatoblastom...mentioning

confidence: 99%

A rare case of hepatoblastoma in a syndromic child with a de novo germline JAG1 mutation

Dangoni

Teixeira

Aguiar

et al. 2023

Pediatric Blood & Cancer

View full text Add to dashboard Cite

“…Mothers against decapentaplegic homolog 3 (Smad3) protein conduct as a signal transduction and transcriptional regulator that mediate a variety of signaling pathways (Kim et al, 2022). Smad3 plays protumorigenic roles in various tumors.…”

Section: Introductionmentioning

confidence: 99%

(E)‐SIS3 suppressed osteosarcoma progression via promoting cell apoptosis, arresting cell cycle, and regulating the tumor immune microenvironment

Huang,

Zhang,

Zhu

et al. 2023

Drug Development Research

View full text Add to dashboard Cite

Osteosarcoma is a prevalent malignant bone tumor with a poor prognosis. Mothers against decapentaplegic homolog 3 (Smad3) present as a therapeutic target in antitumor treatment, whereas its functions in the osteosarcoma have not been well explored. In the current study, we aimed to investigate the effects of Smad3 in the progression of osteosarcoma. The tumor immune single‐cell hub 2 website was used for graph‐based visualization of Smad3 status in osteosarcoma single‐cell database. Western Blot was applied to detect the expression of Smad3 protein in cell lines. Colony formation and cell counting kit‐8 assays were used to evaluate cell proliferation. Transwell and wound healing assays were used to detect the migration and invasion abilities of cells. Cell apoptosis rates and cell cycle changes were explored by using flow cytometry analysis. The xenograft tumor growth model was applied to explore the effect in tumor growth after Smad3 blockage in vivo. Moreover, to confirm the potential mechanism of Smad3's effects on osteosarcoma, bioinformatics analysis was performed in TARGET‐Osteosarcoma and GSE19276 databases. Our study found that the Smad3 protein is overexpressed in 143B and U2OS cells, suppressing the expression of Smad3 protein in osteosarcoma cells by Smad3 target inhibitor (E)‐SIS3 or lentivirus can inhibit the proliferation, migration, invasion, promote cell apoptosis, arrest cell G1 cycle in osteosarcoma cells in vitro, and suppress tumor growth in vivo. Furthermore, the bioinformatics analysis demonstrated that high expression of Smad3 is closely associated with low immune status in TARGET‐Osteosarcoma and GSE19276 databases. Our study suggested that Smad3 could contribute positively to osteosarcoma progression via the regulation of tumor immune microenvironment, and Smad3 may represent as an valuable potential therapeutic target in osteosarcoma therapy.

show abstract

The oncogenic JAG1 intracellular domain is a transcriptional cofactor that acts in concert with DDX17/SMAD3/TGIF2

Cited by 8 publications

References 64 publications

Jagged1 intracellular domain/SMAD3 complex transcriptionally regulates TWIST1 to drive glioma invasion

Jagged1 intracellular domain/SMAD3 complex transcriptionally regulates TWIST1 to drive glioma invasion

A rare case of hepatoblastoma in a syndromic child with a de novo germline JAG1 mutation

(E)‐SIS3 suppressed osteosarcoma progression via promoting cell apoptosis, arresting cell cycle, and regulating the tumor immune microenvironment

Contact Info

Product

Resources

About