Cell Migration and Breast Cancer Metastasis in Biomimetic Extracellular Matrices with Independently Tunable Stiffness

2020 ◽  
Vol 30 (49) ◽  
pp. 2005383
Author(s):  
Jyothsna Vasudevan ◽  
Chwee Teck Lim ◽  
Javier G Fernandez
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Extracellular Matrices ◽  
Tunable Stiffness

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 Tumor cell migration screen identifies SRPK1 as breast cancer metastasis determinant

2015 ◽  
Vol 125 (4) ◽  
pp. 1648-1664 ◽  
Author(s):  
Wies van Roosmalen ◽  
Sylvia E. Le Dévédec ◽  
Ofra Golani ◽  
Marcel Smid ◽  
Irina Pulyakhina ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Tumor Cell ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Tumor Cell Migration

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.

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 The SHCA adapter protein cooperates with lipoma-preferred partner in the regulation of adhesion dynamics and invadopodia formation

2020 ◽  
Vol 295 (31) ◽  
pp. 10535-10559 ◽  
Author(s):  
Alex Kiepas ◽  
Elena Voorand ◽  
Julien Senecal ◽  
Ryuhjin Ahn ◽  
Matthew G. Annis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cancer Metastasis ◽  
Transforming Growth Factor ◽  
Adaptor Protein ◽  
Breast Cancer Metastasis ◽  
Cytoskeletal Proteins ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Tirf Microscopy

SHC adaptor protein (SHCA) and lipoma-preferred partner (LPP) mediate transforming growth factor β (TGFβ)-induced breast cancer cell migration and invasion. Reduced expression of either protein diminishes breast cancer lung metastasis, but the reason for this effect is unclear. Here, using total internal reflection fluorescence (TIRF) microscopy, we found that TGFβ enhanced the assembly and disassembly rates of paxillin-containing adhesions in an SHCA-dependent manner through the phosphorylation of the specific SHCA tyrosine residues Tyr-239, Tyr-240, and Tyr-313. Using a BioID proximity labeling approach, we show that SHCA exists in a complex with a variety of actin cytoskeletal proteins, including paxillin and LPP. Consistent with a functional interaction between SHCA and LPP, TGFβ-induced LPP localization to cellular adhesions depended on SHCA. Once localized to the adhesions, LPP was required for TGFβ-induced increases in cell migration and adhesion dynamics. Mutations that impaired LPP localization to adhesions (mLIM1) or impeded interactions with the actin cytoskeleton via α-actinin (ΔABD) abrogated migratory responses to TGFβ. Live-cell TIRF microscopy revealed that SHCA clustering at the cell membrane preceded LPP recruitment. We therefore hypothesize that, in the presence of TGFβ, SHCA promotes the formation of small, dynamic adhesions by acting as a nucleator of focal complex formation. Finally, we defined a previously unknown function for SHCA in the formation of invadopodia, a process that also required LPP. Our results reveal that SHCA controls the formation and function of adhesions and invadopodia, two key cellular structures required for breast cancer metastasis.

scholarly journals CXCR3 as a molecular target in breast cancer metastasis: inhibition of tumor cell migration and promotion of host anti-tumor immunity

Oncotarget ◽  
2015 ◽  
Vol 6 (41) ◽  
pp. 43408-43419 ◽  
Author(s):  
Guiquan Zhu ◽  
H. Hannah Yan ◽  
Yanli Pang ◽  
Jiang Jian ◽  
Bhagelu R. Achyut ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Tumor Cell ◽  
Tumor Immunity ◽  
Cancer Metastasis ◽  
Molecular Target ◽  
Breast Cancer Metastasis ◽  
Tumor Cell Migration ◽  
Metastasis Inhibition

scholarly journals Cyclin-dependent kinase-mediated phosphorylation of breast cancer metastasis suppressor 1 (BRMS1) affects cell migration

Cell Cycle ◽  
2016 ◽  
Vol 15 (1) ◽  
pp. 137-151 ◽  
Author(s):  
Siti Nur Ain Roesley ◽  
Randy Suryadinata ◽  
Emma Morrish ◽  
Anthonius Ricardo Tan ◽  
Samah M. A. Issa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Metastasis Suppressor ◽  
Cyclin Dependent Kinase ◽  
Metastasis Suppressor 1 ◽  
Breast Cancer Metastasis Suppressor

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

2019 ◽  
Author(s):  
Daniel P. Hollern ◽  
Matthew R. Swiatnicki ◽  
Jonathan P. Rennhack ◽  
Sean A. Misek ◽  
Brooke C. Matson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Pulmonary Metastasis ◽  
Target Gene ◽  
Cancer Metastasis ◽  
Target Genes ◽  
Cancer Cell Line ◽  
Breast Cancer Metastasis ◽  
E2f Transcription Factors

ABSTRACTIn prior work we demonstrated that loss of E2F transcription factors inhibits metastasis. Here we address the mechanisms for this phenotype and identify the E2F regulated genes that coordinate tumor cell metastasis. Transcriptomic profiling of E2F1 knockout tumors identified a role for E2F1 as a master regulator of a suite of pro-metastatic genes, but also uncovered E2F1 target genes with an unknown role in pulmonary metastasis. High expression of one of these genes, Fgf13, is associated with early human breast cancer metastasis in a clinical dataset. Together these data led to the hypothesis that Fgf13 is critical for breast cancer metastasis, and that upregulation of Fgf13 may partially explain how E2F1 promotes breast cancer metastasis. To test this hypothesis we ablated Fgf13 via CRISPR. Deletion of Fgf13 in a MMTV-PyMT breast cancer cell line reduces the frequency of pulmonary metastasis. In addition, loss of Fgf13 reduced in vitro cell migration, suggesting that Fgf13 may be critical for tumor cells to invade out of and escape the primary tumor. The significance of this work is twofold: we have both uncovered genomic features by which E2F1 regulates metastasis and we have identified new pro-metastatic functions for the E2F1 target gene Fgf13.

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