FOXO3a inhibits the EMT and metastasis of breast cancer by regulating TWIST-1 mediated miR-10b/CADM2 axis

Thymoquinone (TQ) has shown substantial evidence for its anticancer effects. Using human breast cancer cells, we evaluated the chemomodulatory effect of TQ on paclitaxel (PTX). TQ showed weak cytotoxic properties against MCF-7 and T47D breast cancer cells with IC50 values of 64.93 ± 14 µM and 165 ± 2 µM, respectively. Combining TQ with PTX showed apparent antagonism, increasing the IC50 values of PTX from 0.2 ± 0.07 µM to 0.7 ± 0.01 µM and from 0.1 ± 0.01 µM to 0.15 ± 0.02 µM in MCF-7 and T47D cells, respectively. Combination index analysis showed antagonism in both cell lines with CI values of 4.6 and 1.6, respectively. However, resistance fractions to PTX within MCF-7 and T47D cells (42.3 ± 1.4% and 41.9 ± 1.1%, respectively) were completely depleted by combination with TQ. TQ minimally affected the cell cycle, with moderate accumulation of cells in the S-phase. However, a significant increase in Pre-G phase cells was observed due to PTX alone and PTX combination with TQ. To dissect this increase in the Pre-G phase, apoptosis, necrosis, and autophagy were assessed by flowcytometry. TQ significantly increased the percent of apoptotic/necrotic cell death in T47D cells after combination with paclitaxel. On the other hand, TQ significantly induced autophagy in MCF-7 cells. Furthermore, TQ was found to significantly decrease breast cancer-associated stem cell clone (CD44+/CD24-cell) in both MCF-7 and T47D cells. This was mirrored by the downregulation of TWIST-1 gene and overexpression of SNAIL-1 and SNAIL-2 genes. TQ therefore possesses potential chemomodulatory effects to PTX when studied in breast cancer cells via enhancing PTX induced cell death including autophagy. In addition, TQ depletes breast cancer-associated stem cells and sensitizes breast cancer cells to PTX killing effects.

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The correlation between Twist 1 and 2 promoter methylation status and clinicopathologic characteristics of patients with breast cancer

Gene Reports ◽

10.1016/j.genrep.2020.100741 ◽

2020 ◽

Vol 20 ◽

pp. 100741

Author(s):

Maryam Fattahi ◽

Roghayeh Sheervalilou ◽

Nina Hoseinpour ◽

Mohammad Valiloo ◽

Negar Pedram ◽

...

Keyword(s):

Breast Cancer ◽

Promoter Methylation ◽

Methylation Status ◽

Clinicopathologic Characteristics ◽

Promoter Methylation Status ◽

Twist 1

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Upregulation of miR-206 is a potential diagnostic biomarker in breast cancer

Bionatura ◽

10.21931/rb/2021.06.02.15 ◽

2021 ◽

Vol 6 (2) ◽

pp. 1757-1762

Author(s):

Faezeh Karami ◽

Narges Maleki ◽

Arefeh Khazraei Monfared ◽

Sayeh Jafari Marandi

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Cancer Cells ◽

Tumor Cells ◽

Breast Cancer Cells ◽

Culture Medium ◽

Expression Level ◽

Tamoxifen Treatment ◽

Fibroblast Cells ◽

Twist 1

Breast cancer is one of the most common malignancies, and like most cancers, most cases are caused by somatic mutations. Due to estrogen's role in the growth, differentiation, and division of breast and endometrial cancer cells, tamoxifen is used as an estrogen receptor antagonist in breast cancer cells with estrogen receptor (ER +) has a special place, which unfortunately in one-third of the Cases are resisted. This study aimed to investigate the effect of tamoxifen-treated tumor-derived exosomes on the expression pattern of Twist and Bcl-2 oncogenic genes in fibroblast cells. MCF-7 breast cancer cell line and fibroblast cells were purchased and cultured in a complete culture medium. After the appropriate number of cells was reached, they were treated with the appropriate concentration of tamoxifen. Cellular supernatant was then gathered in flasks, and exosomes were extracted from them. After extracting RNA from exosomes and cDNA synthesis, the expression level of miR-206, Twist-1, and Bcl-2 genes were evaluated using the Real-Time PCR method. The electronic microscope results confirmed the correctness of the exosomes isolated from the tumor cell culture medium. It has also been shown that tamoxifen treatment increases the expression of miR-206 in exosomes derived from breast tumor cells. The control group which has been kept untreated induced the expression level of Twist-1 and Bcl-2 genes time-dependently. However, when tamoxifen-treated tumor-derived exosomes treated the target cells, the expression level of oncogenic miRs Twist-1 and Bcl-2 were declined over time. Overall, this study showed that tamoxifen treatment on breast cancer cells could apply its antioncogenic effects on tumor stromal cells, such as fibroblasts, by altering the expression levels of exosomal microRNAs in tumor cells.

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Establishment of twist-1 and TGFBR2 as direct targets of microRNA-20a in mesenchymal to epithelial transition of breast cancer cell-line MDA-MB-231

Experimental Cell Research ◽

10.1016/j.yexcr.2017.10.005 ◽

2017 ◽

Vol 361 (1) ◽

pp. 85-92 ◽

Cited By ~ 9

Author(s):

Soumasree De ◽

Sayantani Das ◽

Srimoyee Mukherjee ◽

Sainy Das ◽

Sumita Sengupta (Bandyopadhyay)

Keyword(s):

Breast Cancer ◽

Cell Line ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Breast Cancer Cell Line ◽

Cancer Cell Line ◽

Mesenchymal To Epithelial Transition ◽

Twist 1

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Abstract 4150: CK-19, MAGE-A3, HER-2 and TWIST-1 expression by RT-qPCR in CTCs of primary breast cancer patients after positive immune-magnetic selection using anti-EpCAM and anti-MUC1 magnetic beads

10.1158/1538-7445.am2011-4150 ◽

2011 ◽

Author(s):

Areti Strati ◽

Athina Markou ◽

Oliver Hoffmann ◽

Rainer Kimmig ◽

Evi S. Lianidou ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Primary Breast Cancer ◽

Magnetic Beads ◽

Breast Cancer Patients ◽

Her 2 ◽

Twist 1

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Mechanisms of Twist 1-Induced Invasion in Breast Cancer Metastasis

10.21236/ada548155 ◽

2011 ◽

Author(s):

Mark Eckert

Keyword(s):

Breast Cancer ◽

Cancer Metastasis ◽

Breast Cancer Metastasis ◽

Twist 1

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Dysregulated JAK2 expression by TrkC promotes metastasis potential, and EMT program of metastatic breast cancer

Scientific Reports ◽

10.1038/srep33899 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 20

Author(s):

Min Soo Kim ◽

Joon Jeong ◽

Jeongbeob Seo ◽

Hae-Suk Kim ◽

Seong-Jin Kim ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Epithelial Mesenchymal Transition ◽

Metastatic Breast ◽

Metastatic Potential ◽

Tumor Formation ◽

Breast Cancers ◽

Autocrine Loop ◽

Mesenchymal Transition ◽

Twist 1

Abstract Metastatic breast cancers are aggressive tumors associated with high levels of epithelial-mesenchymal transition (EMT) markers, activation of IL6/JAK2/STAT3 and PI3K/AKT pathways for cell growth, mobility, invasion, metastasis, and CSC status. We identified a new molecular and functional network present in metastasis that regulates and coordinates with TrkC. Inhibition of SOCS3-mediated JAK2 degradation by TrkC increases total JAK2/STAT3 expression, and then leads to upregulation of Twist-1 through activation of JAK2/STAT3 cascade. Also, TrkC increases secretion and expression of IL-6, suggesting that this autocrine loop generated by TrkC maintains the mesenchymal state by continued activation of the JAK2/STAT3 cascade and upregulation of Twist expression. Moreover, TrkC interacts with the c-Src/Jak2 complex, which increases Twist-1 and Twist-2 levels via regulation of JAK2/STAT3 activation and JAK2/STAT3 expression. Furthermore, TrkC enhances metastatic potential of breast cancer via induction of EMT by upregulating Twist-1 and Twist-2. Additionally, TrkC significantly enhances the ability of breast cancer cells to form pulmonary metastases and primary tumor formation. Unexpectedly, we found that TrkC expression and clinical breast tumor pathological phenotypes show significant correlation. These findings suggest that TrkC plays a central role in tumorigenicity, metastasis, and self-renewal traits of metastatic breast cancer.

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