NDR1 activates CD47 transcription by increasing protein stability and nuclear location of ASCL1 to enhance cancer stem cell properties and evasion of phagocytosis in small cell lung cancer

Wang, Lingling; Wan, Xiaomin; Wang, Tao-Li; Liu, Chun-Qi; Zheng, Fei-Meng

doi:10.1007/s12032-022-01859-w

Cited by 3 publications

(4 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been shown that protein stability and nuclear localization of ASCL47 can activate CD47 transcription (Wang et al . 2022a ). Next, we will further explore the effect of ASCL1-mediated CD47 transcription on hBMSC osteogenic differentiation.…”

Section: Resultsmentioning

confidence: 99%

“…studying small cell lung cancer, it was found that increased protein stability and nuclear localization of ASCL1 activated CD47 transcription, which enhanced cancer stem cell properties and evaded phagocytosis in small cell lung cancer (Wang et al . 2022a ). By searching the JASPAR database ( http://jaspar.genereg.net/ ), we found that ASCL1-binding motif mutations reduced ASCL1-mediated CD47 promoter activity, and the binding of ASCL1 to the promoter region of the CD47 gene in hBMSCs was confirmed using ChIP‒qPCR.…”

Section: Discussionmentioning

confidence: 99%

“…It is worth noting that the stable ASCL1 protein activates CD47 transcription and enhances cancer cell characteristics (Wang et al . 2022a ). In addition, the PDK1 inhibitor BX795 mediates glycolysis in tumor cells by downregulating the PDK1/CD47/AKT signaling pathway (Pai et al .…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Ubiquitination of ASCL1 mediates CD47 transcriptional activation of the AKT signaling pathway, and glycolysis promotes osteogenic differentiation of hBMSCs

Zhang,

Zhu,

Zhou

et al. 2023

In Vitro Cell.Dev.Biol.-Animal

View full text Add to dashboard Cite

Bones are extremely dynamic organs that continually develop and remodel. This process involves changes in numerous gene expressions. hBMSC cells can promote osteogenic differentiation. The purpose of this study was to elucidate the mechanism by which ASCL1 promotes osteogenic differentiation in hBMSC cells while decreasing glycolysis. hBMSCs were induced to differentiate into osteoblasts. The ASCL1 expression level during hBMSC osteogenic differentiation was measured by RT‒qPCR, Western blotting, and immunofluorescence. The differentiation level of osteoblasts was observed after staining with ALP and alizarin red. ChIP-qPCR were used to determine the relationship between ASCL1 and CD47, and the expression of glycolysis-related proteins was detected. Overexpression of ASCL1 was used to determine its impact on osteogenic differentiation. si-USP8 was used to verify the ubiquitination of ASCL1-mediated CD47/AKT pathway’s impact on hBMSC glycolysis and osteogenic differentiation. The results showed that the expression of ASCL1 was upregulated after the induction of osteogenic differentiation in hBMSCs. From a functional perspective, knocking down USP8 can promote the ubiquitination of ASCL1, while the osteogenic differentiation ability of hBMSCs was improved after the overexpression of ASCL1, indicating that ASCL1 can promote the osteogenic differentiation of hBMSCs. In addition, USP8 regulates the ubiquitination level of ASCL1 and mediates CD47 transcriptional regulation of the AKT pathway to increase the glycolysis level of hBMSCs and cell osteogenic differentiation. USP8 ubiquitination regulates the level of ASCL1. In addition, ubiquitination of ASCL1 mediates CD47 transcription to activate the AKT signaling pathway and increase hBMSC glycolysis to promote osteogenic differentiation.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Ubiquitination of ASCL1 mediates CD47 transcriptional activation of the AKT signaling pathway, and glycolysis promotes osteogenic differentiation of hBMSCs

Zhang,

Zhu,

Zhou

et al. 2023

In Vitro Cell.Dev.Biol.-Animal

View full text Add to dashboard Cite

show abstract

“…Conversely, the KRAS-STAT3-miR34a mechanism was described specifically in LUAD but likely applies to other KRAS-driven tumors [164]. MYC is also recurrently amplified and overexpressed in NSCLC and CD47 and is a direct target of MYC-driven transcription [162,224,225]. Given that CD47 is expressed in up to 84% of NSCLC, oncogenes are unlikely to account for CD47 upregulation in all cases.…”

Section: Pathways To Cd47 Upregulation In Nsclcmentioning

confidence: 99%

CD47: The Next Frontier in Immune Checkpoint Blockade for Non-Small Cell Lung Cancer

Lau,

Khavkine Binstock,

Thu

2023

Cancers

View full text Add to dashboard Cite

The success of PD-1/PD-L1-targeted therapy in lung cancer has resulted in great enthusiasm for additional immunotherapies in development to elicit similar survival benefits, particularly in patients who do not respond to or are ineligible for PD-1 blockade. CD47 is an immunosuppressive molecule that binds SIRPα on antigen-presenting cells to regulate an innate immune checkpoint that blocks phagocytosis and subsequent activation of adaptive tumor immunity. In lung cancer, CD47 expression is associated with poor survival and tumors with EGFR mutations, which do not typically respond to PD-1 blockade. Given its prognostic relevance, its role in facilitating immune escape, and the number of agents currently in clinical development, CD47 blockade represents a promising next-generation immunotherapy for lung cancer. In this review, we briefly summarize how tumors disrupt the cancer immunity cycle to facilitate immune evasion and their exploitation of immune checkpoints like the CD47–SIRPα axis. We also discuss approved immune checkpoint inhibitors and strategies for targeting CD47 that are currently being investigated. Finally, we review the literature supporting CD47 as a promising immunotherapeutic target in lung cancer and offer our perspective on key obstacles that must be overcome to establish CD47 blockade as the next standard of care for lung cancer therapy.

show abstract

NDR1 mediates PD-L1 deubiquitination to promote prostate cancer immune escape via USP10

Sun,

Fu,

et al. 2024

Preprint

View full text Add to dashboard Cite

Prostate cancer (PCa) is one of the most common male genitourinary system malignancies. The reasons for the poor therapeutic efficacy of anti-PD-L1 immune checkpoint inhibitor therapy in PCa, despite its significant benefits in other cancers, are unclear. NDR1 plays an important role in innate immunity, but its role in tumor immunity and immunotherapy has not been investigated. The role of NDR1 in the immune microenvironment of PCa and the related mechanisms are unknown. Here, we found a positive correlation between NDR1 and PD-L1 expression in PCa. NDR1 significantly inhibited CD8 + T cell infiltration and function and promoted PCa immune escape. More importantly, NDR1 inhibition significantly enhanced CD8 + T cell activation, which enhanced the therapeutic effect of anti-PD-L1. Mechanistic studies revealed that NDR1 inhibits ubiquitination-mediated PD-L1 degradation via the deubiquitinase USP10, upregulates PD-L1, and promotes PCa immune escape. Thus, our study suggests a unique PD-L1 regulatory mechanism underlying PCa immunotherapy failure. The significance of NDR1 in PCa immune escape and its mechanism of action were clarified, and combined NDR1/PD-L1 inhibition was suggested as an approach to boost PCa immunotherapy effectiveness.

show abstract

NDR1 activates CD47 transcription by increasing protein stability and nuclear location of ASCL1 to enhance cancer stem cell properties and evasion of phagocytosis in small cell lung cancer

Cited by 3 publications

References 66 publications

Ubiquitination of ASCL1 mediates CD47 transcriptional activation of the AKT signaling pathway, and glycolysis promotes osteogenic differentiation of hBMSCs

Ubiquitination of ASCL1 mediates CD47 transcriptional activation of the AKT signaling pathway, and glycolysis promotes osteogenic differentiation of hBMSCs

CD47: The Next Frontier in Immune Checkpoint Blockade for Non-Small Cell Lung Cancer

NDR1 mediates PD-L1 deubiquitination to promote prostate cancer immune escape via USP10

Contact Info

Product

Resources

About