scholarly journals Breast Cancer, Chemokines, And Metastasis: A Search for Decoy Ligands of the CXCR4 Receptor

2018 ◽  
Vol 1 (2) ◽  
pp. 1-9
Author(s):  
Gerald J. Mizejewski

Breast cancer (BC) is the leading cause of cancer-related deaths in young to middle-aged women worldwide. Moreover, the survival rate in BC-patients is only 20% when associated with metastatic disease. The high mortality rate observed in BC women with metastatic disease has precipitated a major challenge revealing an unmet need to develop new therapeutic strategies in treating metastatic cancer. One such approach has involved utilization of chemokines and their receptors as therapeutic targets for cancer metastasis. It has been established that a definitive correlation exists between overexpressed CXCR4 malignant cell receptors and cancer cell growth, invasion, and migration. It is also widely accepted that the CXCR4 receptor, complexed to its CXCL12 ligand, plays a major role in establishing migratory pathway gradients for cancer cells migrating to distant tissues/organ sites. It would follow that chemokine decoy ligands, such as peptide antagonists and inhibitors, could serve to induce receptor blockade and impede subsequent intracellular signaling. Such ligands, synthetic and natural, reportedly contribute to reducing cancer cell growth, invasion, adherence, and migration. The present commentary describes several existing synthetic CXCR4 receptor-ligand peptide antagonists and presents a strategy to develop naturally-occurring human protein-derived peptide candidates.

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3593
Author(s):  
Qun Zhang ◽  
Yihong Zhang ◽  
Jie Zhang ◽  
Dan Zhang ◽  
Mengying Li ◽  
...  

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.


2020 ◽  
Vol 21 (13) ◽  
pp. 4652 ◽  
Author(s):  
Chia-Chien Hsieh ◽  
Huai-Hsuan Chiu ◽  
Chih-Hsuan Wang ◽  
Ching-Hua Kuo

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.


2008 ◽  
Vol 68 (21) ◽  
pp. 9087-9095 ◽  
Author(s):  
Adam W. Studebaker ◽  
Gianluca Storci ◽  
Jillian L. Werbeck ◽  
Pasquale Sansone ◽  
A. Kate Sasser ◽  
...  

2011 ◽  
Author(s):  
Inamul Haque ◽  
Snigdha Banerjee ◽  
Kakali Dhar ◽  
Indranil Chattopadhyay ◽  
Amitabha Ray ◽  
...  

2010 ◽  
Author(s):  
Suren Sarkissyan ◽  
Marianna Sarkissyan ◽  
Yanyuan Wu ◽  
H Phillip Koeffler ◽  
Jaydutt V. Vadgama

2021 ◽  
Vol Volume 15 ◽  
pp. 3451-3461
Author(s):  
Ziyu Liu ◽  
Leilei Huang ◽  
Liwei Sun ◽  
Hui Nie ◽  
Yuqi Liang ◽  
...  

2014 ◽  
Vol 232 (4) ◽  
pp. 391-404 ◽  
Author(s):  
Stefano Marastoni ◽  
Eva Andreuzzi ◽  
Alice Paulitti ◽  
Roberta Colladel ◽  
Rosanna Pellicani ◽  
...  

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