scholarly journals Loss of BRMS1 Promotes a Mesenchymal Phenotype through NF-κB-Dependent Regulation ofTwist1

2014 ◽  
Vol 35 (1) ◽  
pp. 303-317 ◽  
Author(s):  
Yuan Liu ◽  
Marty W. Mayo ◽  
Aizhen Xiao ◽  
Emily H. Hall ◽  
Elianna B. Amin ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Transforming Growth Factor ◽  
Breast Cancer Metastasis ◽  
Metastasis Suppressor ◽  
Mesenchymal Phenotype ◽  
Mesenchymal Transition ◽  
Metastasis Suppressor 1 ◽  
Promoter Occupancy

Breast cancer metastasis suppressor 1 (BRMS1) is downregulated in non-small cell lung cancer (NSCLC), and its reduction correlates with disease progression. Herein, we investigate the mechanisms through which loss of theBRMS1gene contributes to epithelial-to-mesenchymal transition (EMT). Using a short hairpin RNA (shRNA) system, we show that loss of BRMS1 promotes basal and transforming growth factor beta-induced EMT in NSCLC cells. NSCLC cells expressingBRMS1shRNAs (BRMS1knockdown [BRMS1KD]) display mesenchymal characteristics, including enhanced cell migration and differential regulation of the EMT markers. Mesenchymal phenotypes observed inBRMS1KDcells are dependent on RelA/p65, the transcriptionally active subunit of nuclear factor kappa B (NF-κB). In addition, chromatin immunoprecipitation analysis demonstrates that loss ofBRMS1increasesTwist1promoter occupancy of RelA/p65 K310—a key histone modification associated with increased transcription. Knockdown ofTwist1results in reversal ofBRMS1KD-mediated EMT phenotypic changes. Moreover, in our animal model,BRMS1KD/Twist1KDdouble knockdown cells were less efficient in establishing lung tumors thanBRMS1KDcells. Collectively, this study demonstrates that loss of BRMS1 promotes malignant phenotypes that are dependent on NF-κB-dependent regulation ofTwist1. These observations offer fresh insight into the mechanisms through which BRMS1 regulates the development of metastases in NSCLC.

scholarly journals Parthenolide Inhibits Migration and Reverses the EMT Process in Breast Cancer Cells by Suppressing TGFβ and TWIST1

2021 ◽  
Author(s):  
Hazera Binte Sufian ◽  
Julianna Maria Santos ◽  
Zeina Shreen Khan ◽  
Maliha Tabassum Munir ◽  
MD Khurshidul Zahid ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cell Viability ◽  
Cell Lines ◽  
Transforming Growth Factor Beta ◽  
Cancer Metastasis ◽  
Transforming Growth Factor ◽  
Breast Cancer Metastasis ◽  
Control Treatment ◽  
Mesenchymal Transition

Abstract Breast cancer metastasis is the leading cause of mortality among breast cancer patients. Epithelial to mesenchymal transition (EMT) is a biological process that plays a fundamental role in facilitating breast cancer metastasis. The present study assessed the efficacy of parthenolide (PTL,Tanacetum parthenium) on EMT and its underlying mechanisms in in both lowly metastatic, estrogen-receptor positive, MCF-7 cells and highly metastatic triple-negative MDA-MB-231 cells. Cell viability was determined by MTT (3-(4,5-dimethy lthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. Apoptosis was analyzed by FITC (fluorescein isothiocyanate) annexin V apoptosis detection kit. The monolayer wound scratch assay was employed to evaluate cancer cell migration. Proteins were separated and identified by Western blotting. Gene expression was analyzed by quantitative real-time PCR. PTL treatment significantly reduced cell viability and migration while inducing apoptosis in both cell lines. Also, PTL treatment reverses the EMT process by decreasing the mesenchymal marker vimentin and increasing the epithelial marker E-cadherin compared to the control treatment. Importantly, PTL downregulates TWIST1 (a transcription factor and regulator of EMT) gene expression concomitant with the reduction of transforming growth factor beta (TGFβ) protein and gene expression in both cell lines. Our findings provide insights into the therapeutic potential of PTL to mitigate EMT and breast cancer metastasis. These promising results demand in vivo studies.

scholarly journals Polyphenols Modulating Effects of PD-L1/PD-1 Checkpoint and EMT-Mediated PD-L1 Overexpression in Breast Cancer

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1718
Author(s):  
Samia S. Messeha ◽  
Najla O. Zarmouh ◽  
Karam F. A. Soliman
Keyword(s):  
Breast Cancer ◽  
Transforming Growth Factor Beta ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Antitumor Agents ◽  
Transforming Growth Factor ◽  
Close Association ◽  
Immune Surveillance ◽  
Cell Phenotype ◽  
Mesenchymal Transition

Investigating dietary polyphenolic compounds as antitumor agents are rising due to the growing evidence of the close association between immunity and cancer. Cancer cells elude immune surveillance for enhancing their progression and metastasis utilizing various mechanisms. These mechanisms include the upregulation of programmed death-ligand 1 (PD-L1) expression and Epithelial-to-Mesenchymal Transition (EMT) cell phenotype activation. In addition to its role in stimulating normal embryonic development, EMT has been identified as a critical driver in various aspects of cancer pathology, including carcinogenesis, metastasis, and drug resistance. Furthermore, EMT conversion to another phenotype, Mesenchymal-to-Epithelial Transition (MET), is crucial in developing cancer metastasis. A central mechanism in the upregulation of PD-L1 expression in various cancer types is EMT signaling activation. In breast cancer (BC) cells, the upregulated level of PD-L1 has become a critical target in cancer therapy. Various signal transduction pathways are involved in EMT-mediated PD-L1 checkpoint overexpression. Three main groups are considered potential targets in EMT development; the effectors (E-cadherin and Vimentin), the regulators (Zeb, Twist, and Snail), and the inducers that include members of the transforming growth factor-beta (TGF-β). Meanwhile, the correlation between consuming flavonoid-rich food and the lower risk of cancers has been demonstrated. In BC, polyphenols were found to downregulate PD-L1 expression. This review highlights the effects of polyphenols on the EMT process by inhibiting mesenchymal proteins and upregulating the epithelial phenotype. This multifunctional mechanism could hold promises in the prevention and treating breast cancer.

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