DRAK2 contributes to type 1 diabetes by negatively regulating IL-2 sensitivity to alter regulatory T cell development

Mandarano, Alexandra H; Harris, Tirril; Creasy, Blaine M; Wehenkel, Marie; Duggar, Marygrace; Wilander, Benjamin A.; Mishra, Ashutosh; Crawford, Jeremy Chase; Mullen, Sarah A; Williams, Katherine M.; Pillai, M.R.A.; High, Anthony A.; McGargill, Maureen A.

doi:10.1016/j.celrep.2023.112106

Cited by 3 publications

(1 citation statement)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…DAPK2 participates in apoptosis, autophagy, myeloid differentiation, and erythropoiesis ( 22 , 23 ). Extensive researches have been conducted concerning the association of DRAK2 with the development of type 1 diabetes and non-alcoholic fatty liver disease ( 24 , 25 ). Moreover, DAPK2 is involved in the development of various types of cancer, including acute myeloid leukemia ( 26 ), cutaneous T cell lymphoma ( 27 ), and breast cancer ( 28 ).…”

Section: Introductionmentioning

confidence: 99%

Development of an anoikis-related gene signature and prognostic model for predicting the tumor microenvironment and response to immunotherapy in colorectal cancer

Li,

Weng,

Yang

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

The effect of anoikis-related genes (ARGs) on clinicopathological characteristics and tumor microenvironment remains unclear. We comprehensively analyzed anoikis-associated gene signatures of 1057 colorectal cancer (CRC) samples based on 18 ARGs. Anoikis-related molecular subtypes and gene features were identified through consensus clustering analysis. The biological functions and immune cell infiltration were assessed using the GSVA and ssGSEA algorithms. Prognostic risk score was constructed using multivariate Cox regression analysis. The immunological features of high-risk and low-risk groups were compared. Finally, DAPK2-overexpressing plasmid was transfected to measure its effect on tumor proliferation and metastasis in vitro and in vivo. We identified 18 prognostic ARGs. Three different subtypes of anoikis were identified and demonstrated to be linked to distinct biological processes and prognosis. Then, a risk score model was constructed and identified as an independent prognostic factor. Compared to the high-risk group, patients in the low-risk group exhibited longer survival, higher enrichment of checkpoint function, increased expression of CTLA4 and PD-L1, higher IPS scores, and a higher proportion of MSI-H. The results of RT-PCR indicated that the expression of DAPK2 mRNA was significantly downregulated in CRC tissues compared to normal tissues. Increased DAPK2 expression significantly suppressed cell proliferation, promoted apoptosis, and inhibited migration and invasion. The nude mice xenograft tumor model confirmed that high expression of DAPK2 inhibited tumor growth. Collectively, we discovered an innovative anoikis-related gene signature associated with prognosis and TME. Besides, our study indicated that DAPK2 can serve as a promising therapeutic target for inhibiting the growth and metastasis of CRC.

show abstract

Section: Introductionmentioning

confidence: 99%

Development of an anoikis-related gene signature and prognostic model for predicting the tumor microenvironment and response to immunotherapy in colorectal cancer

Li,

Weng,

Yang

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

show abstract

Structurally diverse terpenoids and their DRAK2 inhibitory activities: A follow-up study on the vulnerable conifer Pseudotsuga forrestii

Zhou,

Huang,

et al. 2024

Journal of Molecular Structure

View full text Add to dashboard Cite

Anti-inflammatory and anti-fibrotic effects of topical pan-JAK inhibitor in a chronic graft-versus- host disease model mouse

Sato,

Asai,

Ogawa

et al. 2024

Preprint

View full text Add to dashboard Cite

Systemic administration of Janus kinase (JAK) inhibitors is effective in treating chronic graft-versus-host disease (cGVHD) but is associated with side effects. Topical drug administration is an effective approach in minimizing these effects. We aimed to demonstrate the efficacy of topical delgocitinib administration in a cGVHD mouse model. Allogenic bone-marrow transplantation (BMT) was performed from B10.D2. to BALB/c mice, leading to cGVHD. cGVHD mice were treated with delgocitinib eye drops or ointments; their samples were analyzed 4 weeks post-BMT. Topical delgocitinib ointment and eye-drop administration significantly increased the meibomian-gland (MG) area and attenuated corneal epithelial damage. Pathological and immunohistochemical analyses revealed a substantial reduction in inflammation and pathological fibrosis of the skin and eyelids in delgocitinib-treated cGVHD mice. Signal transducer and activator of transcription (STAT)1, STAT3, and STAT5A phosphorylation was significantly increased in the back skin and eyelids of vehicle-treated cGVHD mice; topical delgocitinib administration significantly reduced the expression of these phosphorylated STAT molecules. Delgocitinib eye drops significantly attenuated corneal epithelial damage, MG acinar depletion, and inflammatory cells infiltration in cGVHD mouse corneas. The JAK/STAT signaling pathway was significantly upregulated in cGVHD mice. In summary, a topical delgocitinib administration attenuated cGVHD phenotype severity in the skin and eyes of cGVHD mice.

show abstract

DRAK2 contributes to type 1 diabetes by negatively regulating IL-2 sensitivity to alter regulatory T cell development

Cited by 3 publications

References 57 publications

Development of an anoikis-related gene signature and prognostic model for predicting the tumor microenvironment and response to immunotherapy in colorectal cancer

Development of an anoikis-related gene signature and prognostic model for predicting the tumor microenvironment and response to immunotherapy in colorectal cancer

Structurally diverse terpenoids and their DRAK2 inhibitory activities: A follow-up study on the vulnerable conifer Pseudotsuga forrestii

Anti-inflammatory and anti-fibrotic effects of topical pan-JAK inhibitor in a chronic graft-versus- host disease model mouse

Contact Info

Product

Resources

About