scholarly journals Schlafen12 Reduces the Aggressiveness of Triple Negative Breast Cancer through Post-Transcriptional Regulation of ZEB1 That Drives Stem Cell Differentiation

2019 ◽  
pp. 999-1014 ◽  
Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1506
Author(s):  
Narjara Gonzalez Suarez ◽  
Sahily Rodriguez Torres ◽  
Amira Ouanouki ◽  
Layal El Cheikh-Hussein ◽  
Borhane Annabi

Obese subjects have an increased risk of developing triple-negative breast cancer (TNBC), in part associated with the chronic low-grade inflammation state. On the other hand, epidemiological data indicates that increased consumption of polyphenol-rich fruits and vegetables plays a key role in reducing incidence of some cancer types. Here, we tested whether green tea-derived epigallocatechin-3-gallate (EGCG) could alter adipose-derived mesenchymal stem cell differentiation into adipocytes, and how this impacts the secretome profile and paracrine regulation of the TNBC invasive phenotype. Here, cell differentiation was performed and conditioned media (CM) from preadipocytes and mature adipocytes harvested. Human TNBC-derived MDA-MB-231 real-time cell migration was performed using the exCELLigence system. Differential gene arrays and RT-qPCR were used to assess gene expression levels. Western blotting was used to assess protein expression and phosphorylation status levels. In vitro vasculogenic mimicry (VM) was assessed with Matrigel. EGCG was found to inhibit the induction of key adipogenic biomarkers, including lipoprotein lipase, adiponectin, leptin, fatty acid synthase, and fatty acid binding protein 4. Increased TNBC-derived MDA-MB-231 cell chemotaxis and vasculogenic mimicry were observed in response to mature adipocytes secretome, and this was correlated with increased STAT3 phosphorylation status. This invasive phenotype was prevented by EGCG, the JAK/STAT inhibitors Tofacitinib and AG490, as well as upon STAT3 gene silencing. In conclusion, dietary catechin-mediated interventions could, in part through the inhibition of adipogenesis and modulation of adipocytes secretome profile, prevent the onset of an obesogenic environment that favors TNBC development.


Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1303
Author(s):  
Rizwan Ali ◽  
Hajar Al Zahrani ◽  
Tlili Barhoumi ◽  
Alshaimaa Alhallaj ◽  
Abdullah Mashhour ◽  
...  

In vitro studies of a disease are key to any in vivo investigation in understanding the disease and developing new therapy regimens. Immortalized cancer cell lines are the best and easiest model for studying cancer in vitro. Here, we report the establishment of a naturally immortalized highly tumorigenic and triple-negative breast cancer cell line, KAIMRC2. This cell line is derived from a Saudi Arabian female breast cancer patient with invasive ductal carcinoma. Immunocytochemistry showed a significant ratio of the KAIMRC2 cells’ expressing key breast epithelial and cancer stem cells (CSCs) markers, including CD47, CD133, CD49f, CD44, and ALDH-1A1. Gene and protein expression analysis showed overexpression of ABC transporter and AKT-PI3Kinase as well as JAK/STAT signaling pathways. In contrast, the absence of the tumor suppressor genes p53 and p73 may explain their high proliferative index. The mice model also confirmed the tumorigenic potential of the KAIMRC2 cell line, and drug tolerance studies revealed few very potent candidates. Our results confirmed an aggressive phenotype with metastatic potential and cancer stem cell-like characteristics of the KAIMR2 cell line. Furthermore, we have also presented potent small molecule inhibitors, especially Ryuvidine, that can be further developed, alone or in synergy with other potent inhibitors, to target multiple cancer-related pathways.


PLoS ONE ◽  
2014 ◽  
Vol 9 (9) ◽  
pp. e107616 ◽  
Author(s):  
Jae Young So ◽  
Janice J. Lin ◽  
Joseph Wahler ◽  
Karen T. Liby ◽  
Michael B. Sporn ◽  
...  

Author(s):  
Appalaraju Jaggupilli ◽  
Stanley Ly ◽  
Khoa Nguyen ◽  
Vivek Anand ◽  
Bin Yuan ◽  
...  

Author(s):  
C Bartholomeusz ◽  
H Saso ◽  
A Dadbin ◽  
K Kazuharu ◽  
GN Hortobagyi

2013 ◽  
Author(s):  
Silvana Aparecida Alves Correa-Noronha ◽  
Maria de Nazareth Gamboa Ritto ◽  
Eduardo Henrique da Silva Freitas ◽  
Maria Del Carmen Molina Wolgien ◽  
Ismael Dale Cotrim Guerreiro da Silva ◽  
...  

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