Role of Dusp6 Phosphatase as a Tumor Suppressor in Non-Small Cell Lung Cancer

Moncho-Amor, Verónica; Pintado‐Berninches, Laura; Cáceres, Inmaculada Ibáñez de; Martín-Villar, Ester; Quintanilla, Miguel; Chakravarty, Probir; Cortes-Sempere, María; Fernández-Varas, Beatriz; Rodriguez-Antolín, Carlos; Castro, Javier de; Sastre, Leandro; Perona, Rosario

doi:10.3390/ijms20082036

Cited by 20 publications

(14 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Multiple reports have shown that dual-specificity phosphatase 6 (Dusp6), an ERK phosphatase, attenuates ERK signaling by the dephosphorylation of ERK. 10,11 Consistent with these studies, DUSP6 has been found to be downregulated in clinical lung tissues. 12 However, how the expression of DUSP6 is regulated remains unknown.…”

Section: Introductionsupporting

confidence: 56%

ZNF251 promotes the progression of lung cancer by activating ERK signaling

et al. 2020

View full text Add to dashboard Cite

Aberrant activation of ERK signaling is a hallmark of lung cancer. Although constitutively activating mutations of EGFR and KRAS contribute to the hyperactivation of ERK1/2, other mechanisms remain elusive. In this study, the zinc finger protein ZNF251 was found to be upregulated in clinical lung cancer samples, and it promoted the growth of lung cancer cells and the growth of primary lung KPC cells from mouse models (Ad‐Cre, KrasG12D, and P53f/f). In studying the molecular mechanism, ZNF251 was found to inhibit the expression of dual‐specificity phosphatase 6, a negative regulator of ERK activation, by directly binding to its promoter region. Taken together, our data indicate the tumor‐promoting effects of ZNF251 in lung cancer and suggest that ZNF251 is a therapeutic target.

show abstract

Section: Introductionsupporting

confidence: 56%

ZNF251 promotes the progression of lung cancer by activating ERK signaling

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The ratio of albumin-to-fibrinogen has been used as a biomarker to judge the clinical prognosis of patients with NSCLS ( 25 ). Studies have reported that the ERK1 signaling pathway plays a key role in promoting the proliferation of NSCLC mesenchymal stem cells ( 26 , 27 ). As such, blocking the ERK signaling pathway improves the therapeutic response of patients with NSCLC to EGFR inhibitors ( 28 ).…”

Section: Discussionmentioning

confidence: 99%

Network pharmacology‑based study to explore the mechanism of the Yiqi Gubiao pill in lung cancer treatment

Zheng

Jing

et al. 2021

Oncol Lett

View full text Add to dashboard Cite

Lung cancer (LC) has been one of the most prevalent and fatal malignancies in the past 5 years. Yiqi Gubiao pills have a good clinical effect against LC. However, their complex composition limits proper understanding of their pharmacological mechanism. Therefore, the present study aimed to systemically explore the underlying mechanisms of Yiqi Gubiao pills in treatment of LC. The network pharmacology approach was employed to identify the active ingredients and LC targets associated with Yiqi Gubiao pills. Prediction of potential active ingredients and action targets was then conducted through protein-protein interaction (PPI), Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. In vitro experiments were then performed to further verify the mechanism of action of Yiqi Gubiao pills, revealing that the anti-LC effects were mediated by regulating the expression of IL6, TP53, albumin (ALB), MAPK3 and AKT1. In total, 102 active ingredients and 229 targets of Yiqi Gubiao pills were identified. The PPI network further revealed that AKT1, TP53, ALB, IL6 and MAPK3 were the top five hub genes associated with LC treatment. Targets of the Yiqi Gubiao pills were mainly enriched in the PI3K-Akt and Advanced glycation end products (AGE)-receptors for AGEs (RAGE) signaling pathways. Overall, network pharmacology deciphered the active ingredients and potential targets of the Yiqi Gubiao pills. Yiqi Gubiao pills partially inhibited the progression of LC by regulating the expression of hub genes (AKT1, TP53, ALB, IL6 and MAPK3) through the PI3K-Akt and AGE-RAGE signaling pathways. The findings of the present study may provide a theoretical basis for the clinical application of Yiqi Gubiao pills in LC treatment.

show abstract

“…It has recently been shown that ERK5 was an essential target of DUSP6 in the H460 NSCLC cell line. Downregulation of DUSP6 enhanced ERK5 activation and EMT, and forced expression of DUSP6 decreased ERK5 activation and EMT characteristics of NSCLC cells, accompanied with respective changes in cell morphology, migration, and adhesion to the extracellular matrix (ECM) [ 60 ].…”

Section: Mechanisms Of Emt Regulated By Erk5mentioning

confidence: 99%

Molecular Mechanisms of Epithelial to Mesenchymal Transition Regulated by ERK5 Signaling

et al. 2021

View full text Add to dashboard Cite

Extracellular signal-regulated kinase (ERK5) is an essential regulator of cancer progression, tumor relapse, and poor patient survival. Epithelial to mesenchymal transition (EMT) is a complex oncogenic process, which drives cell invasion, stemness, and metastases. Activators of ERK5, including mitogen-activated protein kinase 5 (MEK5), tumor necrosis factor α (TNF-α), and transforming growth factor-β (TGF-β), are known to induce EMT and metastases in breast, lung, colorectal, and other cancers. Several downstream targets of the ERK5 pathway, such as myocyte-specific enhancer factor 2c (MEF2C), activator protein-1 (AP-1), focal adhesion kinase (FAK), and c-Myc, play a critical role in the regulation of EMT transcription factors SNAIL, SLUG, and β-catenin. Moreover, ERK5 activation increases the release of extracellular matrix metalloproteinases (MMPs), facilitating breakdown of the extracellular matrix (ECM) and local tumor invasion. Targeting the ERK5 signaling pathway using small molecule inhibitors, microRNAs, and knockdown approaches decreases EMT, cell invasion, and metastases via several mechanisms. The focus of the current review is to highlight the mechanisms which are known to mediate cancer EMT via ERK5 signaling. Several therapeutic approaches that can be undertaken to target the ERK5 pathway and inhibit or reverse EMT and metastases are discussed.

show abstract

Role of Dusp6 Phosphatase as a Tumor Suppressor in Non-Small Cell Lung Cancer

Cited by 20 publications

References 37 publications

ZNF251 promotes the progression of lung cancer by activating ERK signaling

ZNF251 promotes the progression of lung cancer by activating ERK signaling

Network pharmacology‑based study to explore the mechanism of the Yiqi Gubiao pill in lung cancer treatment

Molecular Mechanisms of Epithelial to Mesenchymal Transition Regulated by ERK5 Signaling

Contact Info

Product

Resources

About