Hypermethylation of CCND2 in Lung and Breast Cancer Is a Potential Biomarker and Drug Target

Lung and breast cancer are the leading causes of mortality in women worldwide. The discovery of molecular alterations that underlie these two cancers and corresponding drugs has contributed to precision medicine. We found that CCND2 is a common target in lung and breast cancer. Hypermethylation of the CCND2 gene was reported previously; however, no comprehensive study has investigated the clinical significance of CCND2 alterations and its applications and drug discovery. Genome-wide methylation and quantitative methylation-specific real-time polymerase chain reaction (PCR) showed CCND2 promoter hypermethylation in Taiwanese breast cancer patients. As compared with paired normal tissues and healthy individuals, CCND2 promoter hypermethylation was detected in 40.9% of breast tumors and 44.4% of plasma circulating cell-free DNA of patients. The western cohort of The Cancer Genome Atlas also demonstrated CCND2 promoter hypermethylation in female lung cancer, lung adenocarcinoma, and breast cancer patients and that CCND2 promoter hypermethylation is an independent poor prognostic factor. The cell model assay indicated that CCND2 expression inhibited cancer cell growth and migration ability. The demethylating agent antroquinonol D upregulated CCND2 expression, caused cell cycle arrest, and inhibited cancer cell growth and migration ability. In conclusion, hypermethylation of CCND2 is a potential diagnostic, prognostic marker and drug target, and it is induced by antroquinonol D.

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High TDP43 expression is required for TRIM16-induced inhibition of cancer cell growth and correlated with good prognosis of neuroblastoma and breast cancer patients

Cancer Letters ◽

10.1016/j.canlet.2016.02.021 ◽

2016 ◽

Vol 374 (2) ◽

pp. 315-323 ◽

Cited By ~ 19

Author(s):

Patrick Y. Kim ◽

Owen Tan ◽

Bing Liu ◽

Toby Trahair ◽

Tao Liu ◽

...

Keyword(s):

Breast Cancer ◽

Cell Growth ◽

Cancer Patients ◽

Cancer Cell ◽

Good Prognosis ◽

Breast Cancer Patients ◽

Cancer Cell Growth

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p66α Suppresses Breast Cancer Cell Growth and Migration by Acting as Co-Activator of p53

Cells ◽

10.3390/cells10123593 ◽

2021 ◽

Vol 10 (12) ◽

pp. 3593

Author(s):

Qun Zhang ◽

Yihong Zhang ◽

Jie Zhang ◽

Dan Zhang ◽

Mengying Li ◽

...

Keyword(s):

Breast Cancer ◽

Cell Growth ◽

Tumor Suppressor ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Target Genes ◽

Cancer Cell Growth ◽

Cell Growth And Migration ◽

Breast Cancer Cell Growth ◽

And Migration

p66α is a GATA zinc finger domain-containing transcription factor that has been shown to be essential for gene silencing by participating in the NuRD complex. Several studies have suggested that p66α is a risk gene for a wide spectrum of diseases such as diabetes, schizophrenia, and breast cancer; however, its biological role has not been defined. Here, we report that p66α functions as a tumor suppressor to inhibit breast cancer cell growth and migration, evidenced by the fact that the depletion of p66α results in accelerated tumor growth and migration of breast cancer cells. Mechanistically, immunoprecipitation assays identify p66α as a p53-interacting protein that binds the DNA-binding domain of p53 molecule predominantly via its CR2 domain. Depletion of p66α in multiple breast cells results in decreased expression of p53 target genes, while over-expression of p66α results in increased expression of these target genes. Moreover, p66α promotes the transactivity of p53 by enhancing p53 binding at target promoters. Together, these findings demonstrate that p66α is a tumor suppressor by functioning as a co-activator of p53.

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Abstract B121: AIB1 is a transcriptional and translational mediator of breast cancer cell growth and migration targets

10.1158/1557-3125.advbc-b121 ◽

2013 ◽

Author(s):

Aleksandra M. Ochnik ◽

Mark S. Peterson ◽

Svetlana V. Avdulov ◽

Douglas Yee

Keyword(s):

Breast Cancer ◽

Cell Growth ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Cancer Cell Growth ◽

Cell Growth And Migration ◽

Breast Cancer Cell Growth ◽

And Migration

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Aspirin Modifies Inflammatory Mediators and Metabolomic Profiles and Contributes to the Suppression of Obesity-Associated Breast Cancer Cell Growth

International Journal of Molecular Sciences ◽

10.3390/ijms21134652 ◽

2020 ◽

Vol 21 (13) ◽

pp. 4652 ◽

Cited By ~ 3

Author(s):

Chia-Chien Hsieh ◽

Huai-Hsuan Chiu ◽

Chih-Hsuan Wang ◽

Ching-Hua Kuo

Keyword(s):

Breast Cancer ◽

Oxidative Stress ◽

Fatty Acid ◽

Cell Growth ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Cancer Cell Growth ◽

Cell Growth And Migration ◽

Breast Cancer Cell Growth ◽

And Migration

Breast cancer is the most common cancer among women. Adiposity generally accompanies immune cell infiltration and cytokine secretion, which is ideal for tumor development. Aspirin is a chemopreventive agent against several types of cancer. The aim of this study was to investigate whether aspirin inhibits the growth of 4T1 breast cancer cells by inhibiting the inflammatory response and regulating the metabolomic profile of 3T3-L1 adipocytes. 3T3-L1 adipocyte-conditioned medium (Ad-CM) was used to mimic the obese adipose tissue microenvironment in 4T1 cells. The results revealed that aspirin inhibited macrophage chemoattractant protein (MCP-1), interleukin (IL-6), IL-1β, and plasminogen activator inhibitor (PAI-1) production in 3T3-L1 adipocytes stimulated by tumor necrosis factor-alpha (TNF-α) and lipopolysaccharide (LPS). In the obesity-associated model, Ad-CM significantly promoted 4T1 cell growth and migration, which were attenuated after aspirin treatment. The results of metabolic analyses using Ad-CM showed that amino acid metabolites and oxidative stress were increased in mature 3T3-L1 adipocytes compared to those in fibroblasts. Aspirin treatment modified metabolites involved in suppressing lipogenesis, oxidative stress, and neoplastic formation. In the relative fatty acid quantitation analysis of Ad-CM, aspirin diminished fatty acid contents of C16:1, C18:1, C18:2, C20:4, and C24:1. This study is the first to show that aspirin modifies the metabolomics and fatty acid composition of 3T3-L1 adipocytes and inhibits obesity-associated inflammation that contributes to obesity-related breast cancer cell growth and migration.

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