Inhibition of Tyrosine 3-Monooxygenase/Tryptophan 5-Monooxygenase Activation Protein Zeta (YWHAZ) Overcomes Drug Resistance and Tumorigenicity in Ovarian Cancer

Hong, Liu; Chen, Wangsheng; Xing, Aiwen; Wu, Dongcai; Wang, Shengtan

doi:10.1159/000492839

Cited by 12 publications

(15 citation statements)

References 31 publications

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“…The tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) was identified in 55.9% of all patients’ combinations from all nine cancer types. This protein is present in high levels in different cancer cells and is associated with tumor cell proliferation, cell invasion and migration, and drug resistance (Nishimura et al, 2013; Hong et al, 2018; Deng et al, 2019). This protein target has prognostic potential, and its overexpression is associated with short OS time in non-squamous-cell lung carcinoma (Deng et al, 2019); its knockdown has suppressed tumorigenesis in ovarian cancer cells (Hong et al, 2018).…”

Section: Resultsmentioning

confidence: 99%

Signaling Complexity Measured by Shannon Entropy and Its Application in Personalized Medicine

et al. 2019

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Traditional approaches to cancer therapy seek common molecular targets in tumors from different patients. However, molecular profiles differ between patients, and most tumors exhibit inherent heterogeneity. Hence, imprecise targeting commonly results in side effects, reduced efficacy, and drug resistance. By contrast, personalized medicine aims to establish a molecular diagnosis specific to each patient, which is currently feasible due to the progress achieved with high-throughput technologies. In this report, we explored data from human RNA-seq and protein–protein interaction (PPI) networks using bioinformatics to investigate the relationship between tumor entropy and aggressiveness. To compare PPI subnetworks of different sizes, we calculated the Shannon entropy associated with vertex connections of differentially expressed genes comparing tumor samples with their paired control tissues. We found that the inhibition of up-regulated connectivity hubs led to a higher reduction of subnetwork entropy compared to that obtained with the inhibition of targets selected at random. Furthermore, these hubs were described to be participating in tumor processes. We also found a significant negative correlation between subnetwork entropies of tumors and the respective 5-year survival rates of the corresponding cancer types. This correlation was also observed considering patients with lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) based on the clinical data from The Cancer Genome Atlas database (TCGA). Thus, network entropy increases in parallel with tumor aggressiveness but does not correlate with PPI subnetwork size. This correlation is consistent with previous reports and allowed us to assess the number of hubs to be inhibited for therapy to be effective, in the context of precision medicine, by reference to the 100% patient survival rate 5 years after diagnosis. Large standard deviations of subnetwork entropies and variations in target numbers per patient among tumor types characterize tumor heterogeneity.

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Section: Resultsmentioning

confidence: 99%

Signaling Complexity Measured by Shannon Entropy and Its Application in Personalized Medicine

et al. 2019

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“…Many previous studies have established a strong relationship between 14 and 3-3 proteins and various cancer types, 48−50 but cysteine modification-related functions have been unclear. However, the 14-3-3 family has emerged as a promising therapeutic target for cancer and neurodegenerative diseases, 51,52 and, therefore, Cys25 and Cys94 of 14-3-3 protein zeta need to be investigated. Peroxiredoxin-1 also plays an important role in cancer development and inflammation.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…Many previous studies have established a strong relationship between 14 and 3-3 proteins and various cancer types, − but cysteine modification-related functions have been unclear. However, the 14-3-3 family has emerged as a promising therapeutic target for cancer and neurodegenerative diseases, , and, therefore, Cys25 and Cys94 of 14-3-3 protein zeta need to be investigated. Peroxiredoxin-1 also plays an important role in cancer development and inflammation. − It is a dual-function protein that acts as both an antioxidant enzyme and molecular chaperone. , Peroxiredoxin-1 has been reported to interact with essential signaling molecules such as p53, NF-κB, and Toll-like receptor 4 (TLR4) .…”

Section: Resultsmentioning

confidence: 99%

Cellular Target Proteome in Breast Cancer Cells of an Oplopane Sesquiterpenoid Isolated fromTussilago farfara

Song

Nho

et al. 2020

J. Nat. Prod.

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Tussilago farfara is a traditional herbal medicine used to treat coughs, bronchitis, and asthma. Its bioactive compounds include sesquiterpenoids with anti-inflammatory, antiproliferative, neuroprotective, and other effects. Biochemical studies have highlighted the mechanisms of action, but the investigations of related molecular pathways have not specified direct molecular targets. Therefore, this study profiled cellular target proteins of a sesquiterpenoid isolated from T. farfara using quantitative chemical proteomics in MDA-MB-231 and MCF-7 human breast cancer cells. Compound 8, 7β-(3′-ethyl-cis-crotonoyloxy)-1α-(2′-methyl butyryloxy)-3,14-dehydro-Z-notonipetranone, exhibited potent antiproliferative activity based on its α,β-unsaturated carbonyl moiety, and its potential cellular target proteins were identified using a compound 8-based clickable probe. Among >200 identified proteins, 17 showed enrichment ratios of >3 in both cell lines, while recombinant 14-3-3 protein zeta and peroxiredoxin-1 were verified using isothermic calorimetry and their alkylation sites. Considering the interaction between the α,β-unsaturated carbonyl moiety of compound 8 and cysteine residues of the proteins, peptides containing Cys25 and Cys94 of 14-3-3 protein zeta and Cys83 of peroxiredoxin-1 were significantly reduced by this sesquiterpene ester. Although the results did not elucidate the effects of compound 8 in breast cancer cells, identification of potential target proteins contributes to enhanced understanding of its antiproliferative and anti-inflammatory effects.

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“…They observed that the knockdown of YWHAZ inhibits cell proliferation, migration, and invasion of gastric cancer cells [44] As Hong et al observed, the YWHAZ downregulation of YWHAZ inhibited cell cycle progression, migration, and the expression of stem cell markers. Moreover, tumorigenicity was suppressed in tumor-bearing BALB/c nude mice following the YWHAZ knockdown [45].…”

Section: Discussionmentioning

confidence: 99%

Analysis of the Antiproliferative Effect of Ankaferd Hemostat on Caco-2 Colon Cancer Cells via LC/MS Shotgun Proteomics Approach

Koçak

Çelebi̇er

Haznedaroğlu

et al. 2019

BioMed Research International

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Ankaferd hemostat (ABS), a traditional herbal extract, is a hemostatic agent used for wound healing and bleeding treatment. A standardized form of plants contains many biomolecules. In recent years, previous studies have demonstrated the antineoplastic effect of ABS. In the present work, we focused on the mechanism of its antineoplastic effect over Caco-2 colon cancer cells. The LC/MS-based proteomics method was used to understand the effect of ABS at the protein level. The results were evaluated with gene ontology, protein interaction, and pathway analysis. As shown by our results, ABS altered glucose, fatty acids, and protein metabolism. Moreover, ABS affects the cell cycle machinery. Moreover, we found that ABS induced critical cancer target and suppressor proteins such as carboxyl-terminal hydrolase 1, 60S ribosomal protein L5, Tumor protein D52-like2, karyopherin alpha 2, and protein deglycase DJ-1. In conclusion, the proteomics results indicated that ABS affects various cancer targets and suppressor proteins. Moreover ABS has systematical effect on cell metabolism and cell cycle in Caco-2 cells, suggesting that it could be used as an antineoplastic agent.

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Inhibition of Tyrosine 3-Monooxygenase/Tryptophan 5-Monooxygenase Activation Protein Zeta (YWHAZ) Overcomes Drug Resistance and Tumorigenicity in Ovarian Cancer

Cited by 12 publications

References 31 publications

Signaling Complexity Measured by Shannon Entropy and Its Application in Personalized Medicine

Signaling Complexity Measured by Shannon Entropy and Its Application in Personalized Medicine

Cellular Target Proteome in Breast Cancer Cells of an Oplopane Sesquiterpenoid Isolated fromTussilago farfara

Analysis of the Antiproliferative Effect of Ankaferd Hemostat on Caco-2 Colon Cancer Cells via LC/MS Shotgun Proteomics Approach

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