AMPK attenuates SHH subgroup medulloblastoma growth and metastasis by inhibiting NF-κB activation

Cai, Jing; Wang, Yue; Wang, Xinfa; Ai, Zihe; Li, Tianyuan; Pu, Xiaohong; Yang, Xin; Yao, Ye; He, Jinliang; Cheng, Steven Y.; Yu, Tingting; Liu, Chen; Yue, Shen

doi:10.1186/s13578-023-00963-2

Cited by 6 publications

(4 citation statements)

References 34 publications

(35 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, the cellular senescence pathways in multiple malignancies were sensitive to TPCA-1 [ 77 ]. Moreover, TPCA-1 also synergistically restrained the growth, migration, and invasion of medulloblastoma cells by blocking the Sonic hedgehog and NF-κB pathways [ 78 ]. Using transcriptome-based drug repositioning, TPCA-1 was also screened as a potential selective inhibitor of esophagus squamous carcinoma [ 79 ].…”

Section: Discussionmentioning

confidence: 99%

Chemotherapy-elicited extracellular vesicle CXCL1 from dying cells promotes triple-negative breast cancer metastasis by activating TAM/PD-L1 signaling

Wang,

Li,

Hong

et al. 2024

J Exp Clin Cancer Res

View full text Add to dashboard Cite

Background Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, and chemotherapy still serves as the cornerstone treatment functioning by inducing cytotoxic cell death. Notably, emerging evidence suggests that dying cell-released signals may induce cancer progression and metastasis by modulating the surrounding microenvironment. However, the underlying molecular mechanisms and targeting strategies are yet to be explored. Methods Apoptotic TNBC cells induced by paclitaxel or adriamycin treatment were sorted and their released extracellular vesicles (EV-dead) were isolated from the cell supernatants. Chemokine array analysis was conducted to identify the crucial molecules in EV-dead. Zebrafish and mouse xenograft models were used to investigate the effect of EV-dead on TNBC progression in vivo. Results It was demonstrated that EV-dead were phagocytized by macrophages and induced TNBC metastasis by promoting the infiltration of immunosuppressive PD-L1+ TAMs. Chemokine array identified CXCL1 as a crucial component in EV-dead to activate TAM/PD-L1 signaling. CXCL1 knockdown in EV-dead or macrophage depletion significantly inhibited EV-dead-induced TNBC growth and metastasis. Mechanistic investigations revealed that CXCL1EV-dead enhanced TAM/PD-L1 signaling by transcriptionally activating EED-mediated PD-L1 promoter activity. More importantly, TPCA-1 (2-[(aminocarbonyl) amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide) was screened as a promising inhibitor targeting CXCL1 signals in EVs to enhance paclitaxel chemosensitivity and limit TNBC metastasis without noticeable toxicities. Conclusions Our results highlight CXCL1EV-dead as a novel dying cell-released signal and provide TPCA-1 as a targeting candidate to improve TNBC prognosis. Graphical abstract

show abstract

Section: Discussionmentioning

confidence: 99%

Chemotherapy-elicited extracellular vesicle CXCL1 from dying cells promotes triple-negative breast cancer metastasis by activating TAM/PD-L1 signaling

Wang,

Li,

Hong

et al. 2024

J Exp Clin Cancer Res

View full text Add to dashboard Cite

show abstract

“…In addition to the MAPK pathway, the NFKB and TNF pathways were also downregulated in NCI-H295R cells after they were treated with Rottlerin. Studies have already described that AMPK inhibits NFKB and TNF [ 52 , 53 , 54 , 55 ]. However, our transcriptome results must be analyzed with caution, as they were performed in single replicates.…”

Section: Discussionmentioning

confidence: 99%

Low PRKAB2 Expression Is Associated with Poor Outcomes in Pediatric Adrenocortical Tumors, and Treatment with Rottlerin Increases the PRKAB2 Level and Inhibits Tumorigenic Aspects in the NCI-H295R Adrenocortical Cancer Cell Line

Xavier,

Veronez,

Nagano

et al. 2024

Cancers

View full text Add to dashboard Cite

Pediatric adrenocortical tumors (ACTs) are rare, highly heterogeneous neoplasms with limited therapeutic options, making the investigation of new targets with potential therapeutic or prognostic purposes urgent. The PRKAB2 gene produces one of the subunits of the AMP-activated protein kinase (AMPK) complex and has been associated with cancer. However, little is known about the role AMPK plays in ACTs. We have evaluated how PRKAB2 is associated with clinical and biological characteristics in 63 pediatric patients with ACTs and conducted in vitro studies on the human NCI-H295R ACC cell line. An analysis of our cohort and the public ACC pediatric dataset GSE76019 showed that lower PRKAB2 expression was associated with relapse, death, metastasis, and lower event-free and overall survival rates. Multivariate analysis showed that PRKAB2 expression was an independent prognostic factor when associated with age, tumor weight and volume, and metastasis. In vitro tests on NCI-H295R cells demonstrated that Rottlerin, a drug that can activate AMPK, modulated several pathways in NCI-H295R cells, including AMPK/mTOR, Wnt/β-catenin, SKP2, HH, MAPK, NFKB, and TNF. Treatment with Rottlerin decreased cell proliferation and migration, clonogenic capacity, and steroid production. Together, these results suggest that PRKAB2 is a potential prognostic marker in pediatric ACTs, and that Rottlerin is promising for investigating drugs that can act against ACTs.

show abstract

“…The AMPK pathway plays a vital role in maintaining cellular energy homeostasis by activating catabolic processes that generate ATP while inhibiting anabolic processes that consume ATP. Dysregulation of AMPK signaling has been implicated in various diseases, including cancer [62][63][64]. Recent studies have highlighted the significance of PRKAA1 and PRKAA2 in tumorigenesis and cancer progression.…”

Section: Discussionmentioning

confidence: 99%

Variances in the Expression Profile of Circadian Clock-Related Genes in Astrocytic Brain Tumors

Staszkiewicz,

Sobański,

Pulka

et al. 2024

Cancers

View full text Add to dashboard Cite

This study explores the role of circadian clock genes in the progression of astrocytic tumors, a prevalent type of brain tumor. The aim was to assess the expression patterns of these genes in relation to the tumor grade. Using microarray analysis, qRT-PCR, and methylation-specific PCR, we examined gene expression, DNA methylation patterns, and microRNA interactions in tumor samples from 60 patients. Our results indicate that the expression of key circadian clock genes, such as clock circadian regulator (CLOCK), protein kinase AMP-activated catalytic subunit alpha 1 (PRKAA1), protein kinase AMP-activated catalytic subunit alpha 2 (PRKAA2), protein kinase AMP-activated non-catalytic subunit beta 1 (PRKAB1), protein kinase AMP-activated non-catalytic subunit beta 2 (PRKAB2), period circadian regulator 1 (PER1), period circadian regulator 2 (PER2) and period circadian regulator 3 (PER3), varies significantly with the tumor grade. Notably, increased CLOCK gene expression and protein levels were observed in higher-grade tumors. DNA methylation analysis revealed that the promoter regions of PER1-3 genes were consistently methylated, suggesting a mechanism for their reduced expression. Our findings also underscore the complex regulatory mechanisms involving miRNAs, such as hsa-miR-106-5p, hsa-miR-20b-5p, and hsa-miR-30d-3p, which impact the expression of circadian clock-related genes. This underscores the importance of circadian clock genes in astrocytic tumor progression and highlights their potential as biomarkers and therapeutic targets. Further research is needed to validate these results and explore their clinical implications.

show abstract

AMPK attenuates SHH subgroup medulloblastoma growth and metastasis by inhibiting NF-κB activation

Cited by 6 publications

References 34 publications

Chemotherapy-elicited extracellular vesicle CXCL1 from dying cells promotes triple-negative breast cancer metastasis by activating TAM/PD-L1 signaling

Chemotherapy-elicited extracellular vesicle CXCL1 from dying cells promotes triple-negative breast cancer metastasis by activating TAM/PD-L1 signaling

Low PRKAB2 Expression Is Associated with Poor Outcomes in Pediatric Adrenocortical Tumors, and Treatment with Rottlerin Increases the PRKAB2 Level and Inhibits Tumorigenic Aspects in the NCI-H295R Adrenocortical Cancer Cell Line

Variances in the Expression Profile of Circadian Clock-Related Genes in Astrocytic Brain Tumors

Contact Info

Product

Resources

About