The MAPK and AMPK signalings: interplay and implication in targeted cancer therapy

Yuan, Jimin; Dong, Xiaoduo; Yap, Jiajun; Hu, Jiancheng

doi:10.1186/s13045-020-00949-4

Cited by 265 publications

(235 citation statements)

References 285 publications

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“…In this study, Wnt signaling was suppressed following treatment, possibly indicating that Wnt signaling was a critical target of the combination therapy. The Ras/RAF/MEK/ ERK signaling pathway is another best-defined pathway in cancer biology (38). ERKs belong to the MAPK family of kinases, which also comprise of p38MAPK and JNK (39).…”

Section: Discussionmentioning

confidence: 99%

Magnesium in Combinatorial With Valproic Acid Suppressed the Proliferation and Migration of Human Bladder Cancer Cells

Shi

et al. 2020

Front. Oncol.

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Magnesium, the second most predominant intracellular cation, plays a crucial role in many physiological functions; magnesium-based biomaterials have been widely used in clinical application. In a variety of cancer types, the high intracellular concentration of magnesium contributes to cancer initiation and progression. Therefore, we initiated this study to investigate the likelihood of confounding magnesium with cancer therapy. In this study, the anti-tumor activity of magnesium and underlying mechanisms were assessed in bladder cancer both in vitro and in vivo. The results indicated that the proliferation of bladder cancer cells was inhibited by treatment with a high concentration of MgCl2 or MgSO4. The apoptosis, G0/G1 cell cycle arrest, autophagy, and ER stress were promoted following treatment with MgCl2. However, the migratory ability of MgCl2 treated cells was similar to that of control cells, as revealed by the trans-well assay. Besides, no significant difference was observed in the proportion of CD44 or CD133 positive cells between the control and MgCl2 treated cells. Thus, to improve the therapeutic effect of magnesium, VPA was used to treat cancer cells in combination with MgCl2. As expected, combination treatment with MgCl2 and VPA could markedly reduce proliferation, migration, and in vivo tumorigenicity of UC3 cells. Moreover, the Wnt signaling was down-regulated, and ERK signaling was activated in the cells treated with combination treatment. In conclusion, the accurate utilization of MgCl2 in targeting autophagy might be beneficial in cancer therapy. Although further studies are warranted, the combination treatment of MgCl2 with VPA is an effective strategy to improve the outcome of chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Magnesium in Combinatorial With Valproic Acid Suppressed the Proliferation and Migration of Human Bladder Cancer Cells

Shi

et al. 2020

Front. Oncol.

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“…MAPK is a well-studied oncogenic pathway, which counts for nearly 40% of human cancer cases [66]. According to TCGA database, the CD274 mRNA level was significantly positively related to RAS-or MEK-activation scores in NSCLC patients [67].…”

Section: Mitogen-activated Protein Kinase (Mapk)mentioning

confidence: 99%

Regulation of PD-L1 expression in the tumor microenvironment

et al. 2021

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Programmed death-ligand 1 (PD-L1) on cancer cells engages with programmed cell death-1 (PD-1) on immune cells, contributing to cancer immune escape. For multiple cancer types, the PD-1/PD-L1 axis is the major speed-limiting step of the anti-cancer immune response. In this context, blocking PD-1/PD-L1 could restore T cells from exhausted status and eradicate cancer cells. However, only a subset of PD-L1 positive patients benefits from α-PD-1/PD-L1 therapies. Actually, PD-L1 expression is regulated by various factors, leading to the diverse significances of PD-L1 positivity. Understanding the mechanisms of PD-L1 regulation is helpful to select patients and enhance the treatment effect. In this review, we focused on PD-L1 regulators at the levels of transcription, post-transcription, post-translation. Besides, we discussed the potential applications of these laboratory findings in the clinic.

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“…Here, MAPK signaling pathways were specially known to affect various diseases including tumorigenesis. 39 Taken together, the results of GO and KEGG pathway enrichments supported that all of the 20 predicted targets had the characteristics and functions as the therapeutic targets of sinomenine for treating breast cancer.…”

Section: Characteristics and Functions Of Predicted Targets For Treatmentioning

confidence: 73%

Network Pharmacology-Based Approach to Investigate the Molecular Targets of Sinomenine for Treating Breast Cancer

Li¹,

Li²,

Jiang³

et al. 2021

CMAR

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Sinomenine has been known to inhibit the proliferation of breast cancer cells. However, its targets have not been found yet. This study aimed to search for molecular targets of sinomenine for treating breast cancer via network pharmacology. Methods: Potential targets of sinomenine or breast cancer were separately screened from indicated databases. The common targets of both sinomenine and breast cancer were considered as the targets of sinomenine for treating breast cancer. A sinomenine-targetpathway network was constructed based on the obtained results from Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The putative targets of sinomenine were further determined by using protein-protein interaction (PPI) analysis and molecular docking. Finally, the putative targets were verified in vitro and in vivo. Results: Twenty predicted targets were identified through network pharmacological analysis. Gene Ontology (GO) and KEGG pathway enrichment indicated that these predicted targets enriched in the process of MAP kinase activity, VEGF signaling pathway, Relaxin signaling pathway, Growth hormone synthesis, secretion and action. MAPK1, NOS3, NR3C1, NOS1 and NOS2 were further identified as the putative targets by using PPI and molecular docking analysis. Expression of MAPK1, NR3C1, NOS1, NOS2 and NOS3 genes were significantly regulated by sinomenine in both MCF-7 cells and MDA-MB-231 cells. Furthermore, the expression of NR3C1 in human breast cancer specimens was lower than that in para-tumor normal tissues. Meanwhile, the expression of NR3C1 in xenograft tumors was up-regulated after sinomenine treatment. Conclusion: MAPK1, NR3C1, NOS1, NOS2 and NOS3 were identified as the putative targets of sinomenine for treating breast cancer. NR3C1 was preliminarily confirmed as a target of sinomenine in two breast cancer cell lines, xenograft tumor models and human breast cancer specimens. These data indicated that the network pharmacology-based prediction of sinomenine targets for treating breast cancer could be reliable.

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The MAPK and AMPK signalings: interplay and implication in targeted cancer therapy

Cited by 265 publications

References 285 publications

Magnesium in Combinatorial With Valproic Acid Suppressed the Proliferation and Migration of Human Bladder Cancer Cells

Magnesium in Combinatorial With Valproic Acid Suppressed the Proliferation and Migration of Human Bladder Cancer Cells

Regulation of PD-L1 expression in the tumor microenvironment

Network Pharmacology-Based Approach to Investigate the Molecular Targets of Sinomenine for Treating Breast Cancer

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