scholarly journals HER2 Upregulates ATF4 to Promote Cell Migration via Activation of ZEB1 and Downregulation of E-Cadherin

2019 ◽  
Vol 20 (9) ◽  
pp. 2223 ◽  
Author(s):  
Peng Zeng ◽  
Shengnan Sun ◽  
Rui Li ◽  
Zhi-Xiong Xiao ◽  
Hu Chen
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cancer Metastasis ◽  
Growth Factor Receptor ◽  
Breast Cancer Metastasis ◽  
Her2 Positive ◽  
Protein Levels ◽  
Activating Transcription Factor 4 ◽  
Activating Transcription Factor ◽  
E Cadherin

HER2 (human epidermal growth factor receptor 2) activation is critical in breast cancer development. HER2 promotes cell proliferation, angiogenesis, survival, and metastasis by activation of PI3K/Akt, Ras/MEK/ERK, and JAK/STAT pathways. However, beyond these signaling molecules, the key proteins underlining HER2-mediated metastasis remain elusive. ATF4 (Activating transcription factor 4), a critical regulator in unfolded protein response (UPR), is implicated in cell migration and tumor metastasis. In this study, we demonstrate that HER2 upregulated ATF4 expression at both mRNA and protein levels, resulting in cell migration increased. In addition, ATF4 upregulated ZEB1 (Zinc finger E-box-binding homeobox 1) and suppressed E-cadherin expression resulting in promoting cell migration. Restoration of E-cadherin expression effectively inhibited HER2- or ATF4-mediated cell migration. In addition, upregulated expression of ATF4 was found in HER2-positive breast cancer specimens. Together, this study demonstrates that ATF4-ZEB1 is important for HER2-mediated cell migration and suggests that ATF4-ZEB1 may be potential therapeutic targets for breast cancer metastasis.

scholarly journals A Novel SASH1-IQGAP1-E-Cadherin Signal Cascade Mediates Breast Cancer Metastasis

2020 ◽  
Author(s):  
Ding’an Zhou ◽  
Xing Zeng ◽  
Yadong Li ◽  
Zhixiong Wu ◽  
Xin Wan
Keyword(s):  
Breast Cancer ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Signal Cascade ◽  
E Cadherin

scholarly journals E2F1 Drives Breast Cancer Metastasis by Regulating the Target Gene FGF13 and Altering Cell Migration

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Daniel P. Hollern ◽  
Matthew R. Swiatnicki ◽  
Jonathan P. Rennhack ◽  
Sean A. Misek ◽  
Brooke C. Matson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Target Gene ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis

scholarly journals Stromal platelet-derived growth factor receptor-β signaling promotes breast cancer metastasis in the brain

2020 ◽  
pp. canres.3731.2019 ◽  
Author(s):  
Katie A. Thies ◽  
Anisha M. Hammer ◽  
Blake E. Hildreth ◽  
Sarah A. Steck ◽  
Jonathan M. Spehar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Cancer Metastasis ◽  
Growth Factor Receptor ◽  
Breast Cancer Metastasis ◽  
Platelet Derived Growth Factor ◽  
The Brain

Abstract A059: Context-dependent regulation of breast cancer metastasis by E-cadherin and p120-catenin

2013 ◽  
Author(s):  
Ron CJ Schackmann ◽  
Sjoerd Klarenbeek ◽  
Miranda van Amersfoort ◽  
Jos Jonkers ◽  
Paul van Diest ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
P120 Catenin ◽  
Context Dependent ◽  
E Cadherin

The Mitotic Kinase Aurora-A Induces Mammary Cell Migration and Breast Cancer Metastasis by Activating the Cofilin-F-actin Pathway

2010 ◽  
Vol 70 (22) ◽  
pp. 9118-9128 ◽  
Author(s):  
Li-hui Wang ◽  
Jin Xiang ◽  
Min Yan ◽  
Yan Zhang ◽  
Yan Zhao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Aurora A ◽  
Mitotic Kinase ◽  
Mammary Cell

scholarly journals Syndecan-1 facilitates breast cancer metastasis to the brain

2019 ◽  
Author(s):  
Megan R. Sayyad ◽  
Madhavi Puchalapalli ◽  
Natasha G. Vergara ◽  
Sierra Mosticone Wangensteen ◽  
Melvin Moore ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Brain Metastasis ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Cancer Cell Migration ◽  
The Brain

AbstractPurposeAlthough survival rates for patients with localized breast cancer have increased, patients with metastatic breast cancer still have poor prognosis. Understanding key factors involved in promoting breast cancer metastasis is imperative for better treatments. In this study, we investigated the role of syndecan-1 (Sdc1) in breast cancer metastasis.MethodsTo assess the role of Sdc1 in breast cancer metastasis, we silenced Sdc1 expression in the triple-negative breast cancer human MDA-MB-231 cell line and overexpressed it in the mouse mammary carcinoma 4T1 cell line. Intracardiac injections were performed in an experimental mouse metastasis model using both cell lines. In vitro transwell blood-brain barrier (BBB) and brain section adhesion assays were utilized to specifically investigate how Sdc1 promotes brain metastasis. A cytokine array was performed to evaluate differences in the breast cancer cell secretome when Sdc1 was silenced.ResultsSilencing expression of Sdc1 in breast cancer cells significantly reduced metastasis to the brain. Conversely, overexpression of Sdc1 increased metastasis to the brain. We found that the reduction in brain metastases with Sdc1 knockdown was likely due to reduced breast cancer cell migration across the BBB and adhesion to the perivascular regions of the brain. However, there was no change in attachment to brain endothelial cells or astrocytes. Loss of Sdc1 also led to changes in breast cancer cell-secreted cytokines, which may influence the BBB.ConclusionsTaken together, our study demonstrates a role for Sdc1 in promoting breast cancer metastasis to the brain. These findings suggest that Sdc1 supports breast cancer cell migration across the BBB through regulation of cytokines, which may modulate the BBB. Further elucidating this mechanism will allow for the development of therapeutic strategies to combat brain metastasis.

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