P300 promotes migration, invasion and epithelial-mesenchymal transition in a nasopharyngeal carcinoma cell line

Liao, Zhiwei; Zhao, Lei; Cai, Mengli; Xi, Mian; He, Liru; Yu, Fang; Zhou, Tongchong; Liu, Meng‐Zhong

doi:10.3892/ol.2016.5491

Cited by 22 publications

(22 citation statements)

References 26 publications

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“…Currently, it is well recognized that TGF-beta contributes to the metastatic potential of tumor cells through promoting EMT, cell migration, and invasion. [ 33 ] A reported by Liao et al [ 26 ] proved that EP300 enhance EMT through acetylation of Smad2 and Smad3 via the TGF-β signaling pathway, and thus promoted the NPC metastasis, which is similar to the result of our study. In addition, several studies demonstrated an important role for aberrant Wnt signaling in NPC involving diverse cellular processes, including cell migration, hypermethylation, and stemness.…”

Section: Discussionsupporting

confidence: 92%

“…Up-regulated gene EP300 was a core node between DEGs and DEMs target genes in the PPI network. In the study of Liao et al, [ 26 ] result of western blotting showed that EP300 protein was increased expression in NPC cell lines compared with normal nasopharyngeal cells. What's more, upregulation of EP300 promote invasion and metastasis of NPC cells by the induction of epithelial-mesenchymal transition (EMT).…”

Section: Discussionmentioning

confidence: 99%

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Identification of novel biomarkers and small-molecule compounds for nasopharyngeal carcinoma with metastasis

Liu

et al. 2020

Medicine

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The purpose of this study was to investigate novel biomarkers and potential mechanisms in nasopharyngeal carcinoma (NPC) patients with metastasis. Two microarray datasets (GSE103611 and GSE36682) were obtained from GEO database, differentially expressed genes (DEGs) and differentially expressed miRNA (DEMs) were identified, Gene ontology (GO) as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted with DEGs and DEMs targeted genes. Protein–protein interactions (PPI) network of the DEGs and DEMs targeted genes were constructed, furthermore, Connectivity Map (CMap) database was applied to select the potential drugs with therapeutic effects. Overall, we identified 396 upregulated and 19 downregulated DEGs. Additionally, we identified 1 upregulated DEM, miR-135b, and a downregulated DEM, miR-574-5p. Functional enrichment analysis indicated that both DEGs and DEMs targeted genes participated in biological process (BP) of regulation of transcription from RNA polymerase II promoter, DNA-templated positive regulation of transcription, and Epstein-Barr virus infection signaling pathway. Besides, upregulated EP300 gene was a hub node both in DEGs and DEMs target genes. CMap database analysis indicated that sanguinarine, verteporfin, and chrysin are potential drugs for prevention and treatment of NPC metastasis. In summary, the common hub gene, biological process and pathway identified in the study provided a novel insight into the potential mechanism of NPC metastasis. Furthermore, we identified several possible small molecule compounds for treatment of NPC metastasis.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Identification of novel biomarkers and small-molecule compounds for nasopharyngeal carcinoma with metastasis

Liu

et al. 2020

Medicine

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“…p300 inhibition significantly decreased cell migration and invasion in PC3-DR cells and reduced vimentin expression. These findings indicate that p300 is involved in cellular pathways that regulate migration and invasion in PCa and are in concordance with previous studies, where they reported involvement of p300 in migration in nasopharyngeal carcinoma and breast cancer cells (Fermento et al 2014, Liao et al 2017.…”

Section: Discussionsupporting

confidence: 93%

p300 is upregulated by docetaxel and is a target in chemoresistant prostate cancer

Gruber

Ferrone

Puhr

et al. 2020

Endocrine-Related Cancer

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Administration of the microtubule inhibitor docetaxel is a common treatment for metastatic castration-resistant prostate cancer (mCRPC) and results in prolonged patient overall survival. Usually, after a short period of time chemotherapy resistance emerges and there is urgent need to find new therapeutic targets to overcome therapy resistance. The lysine-acetyltransferase p300 has been correlated to prostate cancer (PCa) progression. Here, we aimed to clarify a possible function of p300 in chemotherapy resistance and verify p300 as a target in chemoresistant PCa. Immunohistochemistry staining of tissue samples revealed significantly higher p300 protein expression in patients who received docetaxel as a neoadjuvant therapy compared to control patients. Elevated p300 expression was confirmed by analysis of publicly available patient data, where significantly higher p300 mRNA expression was found in tissue of mCRPC tumors of docetaxel-treated patients. Consistently, docetaxel-resistant PCa cells showed increased p300 protein expression compared to docetaxel-sensitive counterparts. Docetaxel treatment of PCa cells for 72 h resulted in elevated p300 expression. shRNA-mediated p300 knockdown did not alter colony formation efficiency in docetaxel-sensitive cells, but significantly reduced clonogenic potential of docetaxel-resistant cells. Downregulation of p300 in docetaxel-resistant cells also impaired cell migration and invasion. Taken together, we showed that p300 is upregulated by docetaxel, and our findings suggest that p300 is a possible co-target in treatment of chemoresistant PCa.

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“…In agreement with ndings that EP300 increases migratory potential and invasiveness of cancer cells [39], [40], we demonstrated reduced lung colonization and distant metastasis as well as circulating tumor cells via EP300 KD in TNBC cells.…”

Section: Discussionsupporting

confidence: 92%

EP300 Knockdown Reduces Cancer Stem Cell Phenotype, Tumor Growth and Metastasis in Triple Negative Breast Cancer

Ring¹,

Kaur

Lang

2020

Preprint

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Background: Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype with basal features, lacking the expression of receptors targeted successfully in other breast cancer subtypes. Treatment response to adjuvant and neoadjuvant chemotherapy is often short-lived and metastatic spread occurs at higher rates than other subtypes within the first five years after diagnosis. TNBCs exhibit stem cell features and are enriched for cancer stem cell (CSC) populations. E1A Binding Protein P300 (EP300) is a large protein with multiple cellular functions, including as an effector in stem cell biology.Methods: We used a genetic knockdown (KD) model of EP300 in TNBC cell lines to investigate the effect on CSC phenotype, tumor growth and metastasis. Side population assay and tumorsphere suspension culture were used in vitro. Xenograft mouse models were used for in vivo studies. We performed in silico analysis of publicly available gene expression data sets to investigate CSC gene expression and molecular pathways as well as survival outcomes associated with EP300 expression in patients with TNBC and basal-like BC.Results: EP300 KD abolished the CSC phenotype by reducing ABCG2 expression, side population cells and tumorsphere formation capacity in vitro as well as tumor formation in a xenograft mouse model in vivo. Metastatic capacity was markedly reduced in EP300 KD cells in vivo, with no detection of circulating tumor cells. TCGA data analysis demonstrated that genes positively correlated with EP300 expression in TNBC and basal-like BC were associated with CSC biology. Survival analysis demonstrated that EP300 expression predicts poor recurrence free survival in TNBC and basal BC. Conclusion: We report a novel oncogenic role for EP300 in driving CSC phenotype representing a potential target to address tumor initiation and metastatic spread in TNBC and basal-like BC. EP300 might serve as a prognostic marker and potential therapeutic target in TNBC.

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P300 promotes migration, invasion and epithelial-mesenchymal transition in a nasopharyngeal carcinoma cell line

Cited by 22 publications

References 26 publications

Identification of novel biomarkers and small-molecule compounds for nasopharyngeal carcinoma with metastasis

Identification of novel biomarkers and small-molecule compounds for nasopharyngeal carcinoma with metastasis

p300 is upregulated by docetaxel and is a target in chemoresistant prostate cancer

EP300 Knockdown Reduces Cancer Stem Cell Phenotype, Tumor Growth and Metastasis in Triple Negative Breast Cancer

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