DEK promoted EMT and angiogenesis through regulating PI3K/AKT/mTOR pathway in triple-negative breast cancer

Yang, Yang; Gao, Mei‐Hua; Lin, Zhenhua; Chen, Liyan; Jin, Yu; Zhu, Guang; Wang, Yixuan; Jin, Tiefeng

doi:10.18632/oncotarget.21864

Cited by 34 publications

(40 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Positive correlation between DEK, breast cancer and lymph node metastasis have been reported by multiple groups [60][61][62][63][64]. DEK regulate EMT associated with breast cancer metastasis via PI3K/AKT/mTOR pathway in TNBC cells (Fig.…”

Section: Dekmentioning

confidence: 78%

“…A positive correlation with angiogenesis factor VEGF and formation of micro-vessel among a cohort of 58 breast cancer patients further validated the role of DEK in breast cancer [62,65]. This induced expression of DEK positively correlate to poor prognosis in TNBC patients as well in invasive ductal carcinoma patients [62,65]. Additionally, invasive adenocarcinoma patient also exhibited higher expression of DEK [59].…”

Section: Dekmentioning

confidence: 80%

“…Additionally, DEK regulate tumor angiogenesis in breast cancer by binding to the DEK Response Element (DRE) in the VEGF promoter thereby inducing HIF-α and acetyltransferase P300 recruitment within the promoter (Fig. 2) [62]. A positive correlation with angiogenesis factor VEGF and formation of micro-vessel among a cohort of 58 breast cancer patients further validated the role of DEK in breast cancer [62,65].…”

Section: Dekmentioning

confidence: 83%

See 2 more Smart Citations

A three layered histone epigenetics in breast cancer metastasis

2020

View full text Add to dashboard Cite

Thanks to the advancement in science and technology and a significant number of cancer research programs being carried out throughout the world, the prevention, prognosis and treatment of breast cancer are improving with a positive and steady pace. However, a stern thoughtful attention is required for the metastatic breast cancer casesthe deadliest of all types of breast cancer, with a character of relapse even when treated. In an effort to explore the less travelled avenues, we summarize here studies underlying the aspects of histone epigenetics in breast cancer metastasis. Authoritative reviews on breast cancer epigenetics are already available; however, there is an urgent need to focus on the epigenetics involved in metastatic character of this cancer. Here we put forward a comprehensive review on how different layers of histone epigenetics comprising of histone chaperones, histone variants and histone modifications interplay to create breast cancer metastasis landscape. Finally, we propose a hypothesis of integrating histone-epigenetic factors as biomarkers that encompass different breast cancer subtypes and hence could be exploited as a target of larger population.

show abstract

Section: Dekmentioning

confidence: 78%

Section: Dekmentioning

confidence: 80%

Section: Dekmentioning

confidence: 83%

See 1 more Smart Citation

A three layered histone epigenetics in breast cancer metastasis

2020

View full text Add to dashboard Cite

show abstract

“…Metastasis is a programmed multistep process, including cell migration, invasion, and adhesion. The exploration of effective natural compounds targeting EMT and angiogenesis have been the efficient therapeutic approach for the treatment of metastatic cancers (Yang et al, ). Luteolin, a flavonoid that is found in more than 300 plant species, has recently been shown to inhibit a variety of cancers, both in vitro and in vivo, with little to minimal toxicity (Lu et al, ; Ruan et al, ).…”

Section: Discussionmentioning

confidence: 99%

HIF‐1α/VEGF signaling‐mediated epithelial–mesenchymal transition and angiogenesis is critically involved in anti‐metastasis effect of luteolin in melanoma cells

Wang

Shen

et al. 2019

Phytotherapy Research

View full text Add to dashboard Cite

Tumor metastasis is still the leading cause of melanoma mortality. Luteolin, a natural flavonoid, is found in fruits, vegetables, and medicinal herbs. The pharmacological action and mechanism of luteolin on the metastasis of melanoma remain elusive. In this study, we investigated the effect of luteolin on A375 and B16‐F10 cell viability, migration, invasion, adhesion, and tube formation of human umbilical vein endothelial cells. Epithelial–mesenchymal transition (EMT) markers and pivotal molecules in HIF‐1α/VEGF signaling expression were analysed using western blot assays or quantitative real‐time polymerase chain reaction. Results showed that luteolin inhibits cellular proliferation in A375 and B16‐F10 melanoma cells in a time‐dependent and concentration‐dependent manner. Luteolin significantly inhibited the migratory, invasive, adhesive, and tube‐forming potential of highly metastatic A375 and B16‐F10 melanoma cells or human umbilical vein endothelial cells at sub‐IC 50 concentrations, where no significant cytotoxicity was observed. Luteolin effectively suppressed EMT by increased E‐cadherin and decreased N‐cadherin and vimentin expression both in mRNA and protein levels. Further, luteolin exerted its anti‐metastasis activity through decreasing the p‐Akt, HIF‐1α, VEGF‐A, p‐VEGFR‐2, MMP‐2, and MMP‐9 proteins expression. Overall, our findings first time suggests that HIF‐1α/VEGF signaling‐mediated EMT and angiogenesis is critically involved in anti‐metastasis effect of luteolin as a potential therapeutic candidate for melanoma.

show abstract

“…In there present study, these DEGs were closly associated with potential therapeutic targets for TNBC. Previous study (47) has demonstrated that the most prominent signaling pathway that is dysregulated in TNBC is the PI3K/AKT/mTOR signaling pathway. PKC (protein kinase C) is an intracellular effector of the C kinase pathway.…”

Section: Discussionmentioning

confidence: 99%

Molecular mechanism of triple‑negative breast cancer‑associated BRCA1 and the identification of signaling pathways

2019

View full text Add to dashboard Cite

BRAC1 has multiple important interactions with triple-negative breast cancer, the specific molecular characteristics of this interaction, however, have not yet been completely elucidated. By examining cell signaling pathways, important information for comprehending the potential mechanisms of this cancer may become known. The aim of the present study was to identify the effects of BRAC1 and to find the signaling pathway(s) involved in the pathogenic mechanism of triple-negative breast cancer. In this study, GSE27447 microarray data were obtained from the Gene Expression Omnibus (GEO) database of the National Center for Biotechnology Information, and differentially expressed genes (DEGs) from GSE27447 were distinguished by Significant Analysis of Microarray. Gene ontology (GO) analysis was carried out on 132 upregulated and 198 downregulated genes with DAVID. The signaling was forecast by the Kyoto Encyclopedia of Genes and Genomes (KEGG). Transcription factors were recognized by TFatS. The BRAC1 relevant protein-protein interaction networks (PPI) were fixed by STRING and visualized by CytoScape. Overall, the upregulated DEGs, which included CR2, IGHM, PRKCB, CARD11, PLCG2, CD79A, IGKC and CD27, were primarily enriched in the terms associated with immune responses, and the downregulated DEGs, which included STARD3, ALDH8A1, SRD5A3, CACNA1H, UGT2B4, SDR16C5 and MED1, were primarily enriched in the hormone metabolic process. In addition, 13 pathways, such as the B-cell receptor-signaling pathway, the hormone synthesis signaling pathway and the oxytocin-signaling pathway, were chosen. MYC, SP1 and CTNNB1 were determined to be enriched in triple-negative breast cancer. A total of 8 genes were identified to be downregulated in the BRAC1-related PPI network. The results of the present study show a fresh angle on the molecular mechanism of triple-negative breast cancer and indicate a possible target for its treatment.

show abstract

DEK promoted EMT and angiogenesis through regulating PI3K/AKT/mTOR pathway in triple-negative breast cancer

Cited by 34 publications

References 47 publications

A three layered histone epigenetics in breast cancer metastasis

A three layered histone epigenetics in breast cancer metastasis

HIF‐1α/VEGF signaling‐mediated epithelial–mesenchymal transition and angiogenesis is critically involved in anti‐metastasis effect of luteolin in melanoma cells

Molecular mechanism of triple‑negative breast cancer‑associated BRCA1 and the identification of signaling pathways

Contact Info

Product

Resources

About