From Proteomic Mapping to Invasion-Metastasis-Cascade Systemic Biomarkering and Targeted Drugging of Mutant BRAF-Dependent Human Cutaneous Melanomagenesis

Giannopoulou, Aikaterini F.; Velentzas, Athanassios D.; Anagnostopoulos, Athanasios K.; Agalou, Adamantia; Παπανδρεου, Νικολαοσ; Katarachia, Stamatia A.; Koumoundourou, Dimitra G.; Konstantakou, Eumorphia G.; Pantazopoulou, Vasiliki I.; Delis, Anastasios; Michailidi, Maria T.; Valakos, Dimitrios; Chatzopoulos, Dimitris; Syntichaki, Popi; Iconomidou, Vassiliki A.; Tsitsilonis, Ourania E.; Papassideri, Issidora S.; Voutsinas, Gerassimos E.; Hatzopoulos, Polydefkis; Thanos, Dimitris; Beis, Dimitris; Anastasiadou, Ema; Tsangaris, George T.; Stravopodis, Dimitrios J.

doi:10.3390/cancers13092024

Cited by 6 publications

(3 citation statements)

References 344 publications

(626 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…E-cadherin is inhibited by this (Fig. 1 ) [ 45 ]. The expression of TGF ligands can be increased if EMT-TFs are activated, resulting in a positive feedback loop through autocrine signaling that helps cells sustain the expression of EMT programs.…”

Section: Signaling Mechanisms Linked To Cancermentioning

confidence: 99%

Ferroptosis and EMT: key targets for combating cancer progression and therapy resistance

Ren,

Mao,

et al. 2023

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

Iron-dependent lipid peroxidation causes ferroptosis, a form of regulated cell death. Crucial steps in the formation of ferroptosis include the accumulation of ferrous ions (Fe2+) and lipid peroxidation, of which are controlled by glutathione peroxidase 4 (GPX4). Its crucial role in stopping the spread of cancer has been shown by numerous studies undertaken in the last ten years. Epithelial–mesenchymal transition (EMT) is the process by which epithelial cells acquire mesenchymal characteristics. EMT is connected to carcinogenesis, invasiveness, metastasis, and therapeutic resistance in cancer. It is controlled by a range of internal and external signals and changes the phenotype from epithelial to mesenchymal like. Studies have shown that mesenchymal cancer cells tend to be more ferroptotic than their epithelial counterparts. Drug-resistant cancer cells are more easily killed by inducers of ferroptosis when they undergo EMT. Therefore, understanding the interaction between ferroptosis and EMT will help identify novel cancer treatment targets. In-depth discussion is given to the regulation of ferroptosis, the potential application of EMT in the treatment of cancer, and the relationships between ferroptosis, EMT, and signaling pathways associated with tumors. Invasion, metastasis, and inflammation in cancer all include ferroptosis and EMT. The goal of this review is to provide suggestions for future research and practical guidance for applying ferroptosis and EMT in clinical practice.

show abstract

Section: Signaling Mechanisms Linked To Cancermentioning

confidence: 99%

Ferroptosis and EMT: key targets for combating cancer progression and therapy resistance

Ren,

Mao,

et al. 2023

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

show abstract

“…Primary (WM115) and metastatic (WM266-4) cutaneous melanoma cells were developed in the same individual [26]. Cancer progression may be correlated with an increase in the expression of certain proteins [27].…”

Section: Introductionmentioning

confidence: 99%

Hypoxia-Induced Changes in L-Cysteine Metabolism and Antioxidative Processes in Melanoma Cells

Rydz,

Wróbel,

Janik

et al. 2023

Biomolecules

View full text Add to dashboard Cite

This study was performed on human primary (WM115) and metastatic (WM266-4) melanoma cell lines developed from the same individual. The expression of proteins involved in L-cysteine metabolism (sulfurtransferases, and cystathionine β-synthase) and antioxidative processes (thioredoxin, thioredoxin reductase-1, glutathione peroxidase, superoxide dismutase 1) as well as the level of sufane sulfur, and cell proliferation under hypoxic conditions were investigated. Hypoxia in WM115 and WM266-4 cells was confirmed by induced expression of carbonic anhydrase IX and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 by the RT-PCR and Western blot methods. It was shown that, under hypoxic conditions the inhibition of WM115 and WM266-4 melanoma cell proliferation was associated with decreased expression of thioredoxin reductase-1 and cystathionine β-synthase. These two enzymes may be important therapeutic targets in the treatment of melanoma. Interestingly, it was also found that in normoxia the expression and activity of 3-mercaptopyruvate sulfurtransferase in metastatic WM266-4 melanoma cells was significantly higher than in primary melanoma WM115 cells.

show abstract

“…Epithelial–mesenchymal transition (EMT) is a multistep process in which morphological changes occur and is involved in neoplastic invasion, metastasis, embryogenesis and wound healing; during EMT, epithelial cells acquire mesenchymal characteristics and gradually lose their epithelial features[ 6 ]. EMT has been shown to be closely associated with local dissemination and subsequent metastasis of solid tumors[ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Development and validation of an epithelial–mesenchymal transition-related gene signature for predicting prognosis

Zhou¹,

Du²,

Fu³

et al. 2022

WJCC

View full text Add to dashboard Cite

BACKGROUND Currently, there are many therapeutic methods for lung adenocarcinoma (LUAD), but the 5-year survival rate is still only 15% at later stages. Epithelial– mesenchymal transition (EMT) has been shown to be closely associated with local dissemination and subsequent metastasis of solid tumors. However, the role of EMT in the occurrence and development of LUAD remains unclear. AIM To further elucidate the value of EMT-related genes in LUAD prognosis. METHODS Univariate, least absolute shrinkage and selection operator, and multivariate Cox regression analyses were applied to establish and validate a new EMT-related gene signature for predicting LUAD prognosis. The risk model was evaluated by Kaplan–Meier survival analysis, principal component analysis, and functional enrichment analysis and was used for nomogram construction. The potential structures of drugs to which LUAD is sensitive were discussed with respect to EMT-related genes in this model. RESULTS Thirty-three differentially expressed genes related to EMT were found to be highly associated with overall survival (OS) by using univariate Cox regression analysis (log2FC ≥ 1, false discovery rate < 0.001). A prognostic signature of 7 EMT-associated genes was developed to divide patients into two risk groups by high or low risk scores. Kaplan–Meier survival analysis showed that the OS of patients in the high-risk group was significantly poorer than that of patients in the low-risk group ( P < 0.05). Multivariate Cox regression analysis showed that the risk score was an independent risk factor for OS (HR > 1, P < 0.05). The results of receiver operator characteristic curve analysis suggested that the 7-gene signature had a perfect ability to predict prognosis (all area under the curves > 0.5). CONCLUSION The EMT-associated gene signature classifier could be used as a feasible indicator for predicting OS.

show abstract

From Proteomic Mapping to Invasion-Metastasis-Cascade Systemic Biomarkering and Targeted Drugging of Mutant BRAF-Dependent Human Cutaneous Melanomagenesis

Cited by 6 publications

References 344 publications

Ferroptosis and EMT: key targets for combating cancer progression and therapy resistance

Ferroptosis and EMT: key targets for combating cancer progression and therapy resistance

Hypoxia-Induced Changes in L-Cysteine Metabolism and Antioxidative Processes in Melanoma Cells

Development and validation of an epithelial–mesenchymal transition-related gene signature for predicting prognosis

Contact Info

Product

Resources

About