scholarly journals Breast Fibroblasts and ECM Components Modulate Breast Cancer Cell Migration through the Secretion of MMPs in a 3D Microfluidic Co-Culture Model

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1173 ◽  
Author(s):  
Karina M. Lugo-Cintrón ◽  
Max M. Gong ◽  
José M. Ayuso ◽  
Lucas A. Tomko ◽  
David J. Beebe ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Progression ◽  
Cancer Cell Migration ◽  
Migration Distance ◽  
Breast Fibroblasts

The extracellular matrix (ECM) composition greatly influences cancer progression, leading to differential invasion, migration, and metastatic potential. In breast cancer, ECM components, such as fibroblasts and ECM proteins, have the potential to alter cancer cell migration. However, the lack of in vitro migration models that can vary ECM composition limits our knowledge of how specific ECM components contribute to cancer progression. Here, a microfluidic model was used to study the effect of 3D heterogeneous ECMs (i.e., fibroblasts and different ECM protein compositions) on the migration distance of a highly invasive human breast cancer cell line, MDA-MB-231. Specifically, we show that in the presence of normal breast fibroblasts, a fibronectin-rich matrix induces more cancer cell migration. Analysis of the ECM revealed the presence of ECM tunnels. Likewise, cancer-stromal crosstalk induced an increase in the secretion of metalloproteinases (MMPs) in co-cultures. When MMPs were inhibited, migration distance decreased in all conditions except for the fibronectin-rich matrix in the co-culture with human mammary fibroblasts (HMFs). This model mimics the in vivo invasion microenvironment, allowing the examination of cancer cell migration in a relevant context. In general, this data demonstrates the capability of the model to pinpoint the contribution of different components of the tumor microenvironment (TME).

scholarly journals Wnt5a induces ROR1 to recruit cortactin to promote breast-cancer migration and metastasis

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Md Kamrul Hasan ◽  
George F. Widhopf ◽  
Suping Zhang ◽  
Sharon M. Lam ◽  
Zhouxin Shen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Surface Protein ◽  
Cancer Cell Migration ◽  
Breast Cancer Cell Migration ◽  
Promote Breast Cancer

Abstract ROR1 is a conserved oncoembryonic surface protein expressed in breast cancer. Here we report that ROR1 associates with cortactin in primary breast-cancer cells or in MCF7 transfected to express ROR1. Wnt5a also induced ROR1-dependent tyrosine phosphorylation of cortactin (Y421), which recruited ARHGEF1 to activate RhoA and promote breast-cancer-cell migration; such effects could be inhibited by cirmtuzumab, a humanized mAb specific for ROR1. Furthermore, treatment of mice bearing breast-cancer xenograft with cirmtuzumab inhibited cortactin phosphorylation in vivo and impaired metastatic development. We established that the proline at 841 of ROR1 was required for it to recruit cortactin and ARHGEF1, activate RhoA, and enhance breast-cancer-cell migration in vitro or development of metastases in vivo. Collectively, these studies demonstrate that the interaction of ROR1 with cortactin plays an important role in breast-cancer-cell migration and metastasis.

scholarly journals Dietary Antioxidant Trans-Cinnamaldehyde Reduced Visfatin-Induced Breast Cancer Progression: In Vivo and In Vitro Study

Antioxidants ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 625 ◽  
Author(s):  
Yi-Fen Chiang ◽  
Hsin-Yuan Chen ◽  
Ko-Chieh Huang ◽  
Po-Han Lin ◽  
Shih-Min Hsia
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Progression ◽  
Natural Compound ◽  
Cancer Cell Line ◽  
Nad Synthesis

Excessive growth of cancer cells is the main cause of cancer mortality. Therefore, discovering how to inhibit cancer growth is an important research topic. Recently, the newly discovered adipokine, known as nicotinamide phosphoribosyl transferase (NAMPT, visfatin), which has been associated with metabolic syndrome and obesity, has also been found to be a major cause of cancer proliferation. Therefore, inhibition of NAMPT and reduction of Nicotinamide adenine dinucleotide (NAD) synthesis is one strategy for cancer therapy. Cinnamaldehyde (CA), as an antioxidant and anticancer natural compound, may have the ability to inhibit visfatin. The breast cancer cell line and xenograft animal models were treated under different dosages of visfatin combined with CA and FK866 (a visfatin inhibitor) to test for cell toxicity, as well as inhibition of tumor-related proliferation of protein expression. In the breast cancer cell and the xenograft animal model, visfatin significantly increased proliferation-related protein expression, but combination with CA or FK866 significantly reduced visfatin-induced carcinogenic effects. For the first time, a natural compound inhibiting extracellular and intracellular NAMPT has been demonstrated. We hope that, in the future, this can be used as a potential anticancer compound and provide further directions for research.

Synthetic Macrolides that Inhibit Breast Cancer Cell Migration in Vitro

2007 ◽  
Vol 129 (9) ◽  
pp. 2434-2435 ◽  
Author(s):  
Belhu B. Metaferia ◽  
Lin Chen ◽  
Heather L. Baker ◽  
Xin-Yun Huang ◽  
Carole A. Bewley
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Migration ◽  
Breast Cancer Cell Migration

scholarly journals O-GlcNAcylation of MORC2 at threonine 556 by OGT couples TGF-β signaling to breast cancer progression

2022 ◽  
Author(s):  
Ying-Ying Liu ◽  
Hong-Yi Liu ◽  
Tian-Jian Yu ◽  
Qin Lu ◽  
Fang-Lin Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Growth Factor ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Progression ◽  
Breast Cancer Progression ◽  
Migration And Invasion ◽  
Cancer Cell Migration ◽  
Tgf Β1

AbstractMORC family CW-type zinc finger 2 (MORC2) is a newly identified chromatin-remodeling enzyme involved in DNA damage response and gene transcription, and its dysregulation has been linked with Charcot-Marie-Tooth disease, neurodevelopmental disorder, and cancer. Despite its functional importance, how MORC2 is regulated remains enigmatic. Here, we report that MORC2 is O-GlcNAcylated by O-GlcNAc transferase (OGT) at threonine 556. Mutation of this site or pharmacological inhibition of OGT impairs MORC2-mediated breast cancer cell migration and invasion in vitro and lung colonization in vivo. Moreover, transforming growth factor-β1 (TGF-β1) induces MORC2 O-GlcNAcylation through enhancing the stability of glutamine-fructose-6-phosphate aminotransferase (GFAT), the rate-limiting enzyme for producing the sugar donor for OGT. O-GlcNAcylated MORC2 is required for transcriptional activation of TGF-β1 target genes connective tissue growth factor (CTGF) and snail family transcriptional repressor 1 (SNAIL). In support of these observations, knockdown of GFAT, SNAIL or CTGF compromises TGF-β1-induced, MORC2 O-GlcNAcylation-mediated breast cancer cell migration and invasion. Clinically, high expression of OGT, MORC2, SNAIL, and CTGF in breast tumors is associated with poor patient prognosis. Collectively, these findings uncover a previously unrecognized mechanistic role for MORC2 O-GlcNAcylation in breast cancer progression and provide evidence for targeting MORC2-dependent breast cancer through blocking its O-GlcNAcylation.

scholarly journals Anillin regulates breast cancer cell migration, growth, and metastasis by non-canonical mechanisms involving control of cell stemness and differentiation

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Dongdong Wang ◽  
Nayden G. Naydenov ◽  
Mikhail G. Dozmorov ◽  
Jennifer E. Koblinski ◽  
Andrei I. Ivanov
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Tumor Growth And Metastasis

Abstract Background Breast cancer metastasis is driven by a profound remodeling of the cytoskeleton that enables efficient cell migration and invasion. Anillin is a unique scaffolding protein regulating major cytoskeletal structures, such as actin filaments, microtubules, and septin polymers. It is markedly overexpressed in breast cancer, and high anillin expression is associated with poor prognosis. The aim of this study was to investigate the role of anillin in breast cancer cell migration, growth, and metastasis. Methods CRISPR/Cas9 technology was used to deplete anillin in highly metastatic MDA-MB-231 and BT549 cells and to overexpress it in poorly invasive MCF10AneoT cells. The effects of anillin depletion and overexpression on breast cancer cell motility in vitro were examined by wound healing and Matrigel invasion assays. Assembly of the actin cytoskeleton and matrix adhesion were evaluated by immunofluorescence labeling and confocal microscopy. In vitro tumor development was monitored by soft agar growth assays, whereas cancer stem cells were examined using a mammosphere formation assay and flow cytometry. The effects of anillin knockout on tumor growth and metastasis in vivo were determined by injecting control and anillin-depleted breast cancer cells into NSG mice. Results Loss-of-function and gain-of-function studies demonstrated that anillin is necessary and sufficient to accelerate migration, invasion, and anchorage-independent growth of breast cancer cells in vitro. Furthermore, loss of anillin markedly attenuated primary tumor growth and metastasis of breast cancer in vivo. In breast cancer cells, anillin was localized in the nucleus; however, knockout of this protein affected the cytoplasmic/cortical events, e.g., the organization of actin cytoskeleton and cell-matrix adhesions. Furthermore, we observed a global transcriptional reprogramming of anillin-depleted breast cancer cells that resulted in suppression of their stemness and induction of the mesenchymal to epithelial trans-differentiation. Such trans-differentiation was manifested by the upregulation of basal keratins along with the increased expression of E-cadherin and P-cadherin. Knockdown of E-cadherin restored the impaired migration and invasion of anillin-deficient breast cancer cells. Conclusion Our study demonstrates that anillin plays essential roles in promoting breast cancer growth and metastatic dissemination in vitro and in vivo and unravels novel functions of anillin in regulating breast cancer stemness and differentiation.

scholarly journals Arl13b Regulates Breast Cancer Cell Migration and Invasion by Controlling Integrin-Mediated Signaling

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1461 ◽  
Author(s):  
Cristina Casalou ◽  
Alexandra Faustino ◽  
Fernanda Silva ◽  
Inês C. Ferreira ◽  
Daniela Vaqueirinho ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Progression ◽  
Migration And Invasion ◽  
Breast Cancer Cell Lines ◽  
Cancer Cell Migration ◽  
Cell Migration And Invasion ◽  
Breast Cancer Cell Migration

Breast cancer is the first cause of cancer-related mortality among women worldwide, according to the most recent estimates. This mortality is mainly caused by the tumors’ ability to form metastases. Cancer cell migration and invasion are essential for metastasis and rely on the interplay between actin cytoskeleton remodeling and cell adhesion. Therefore, understanding the mechanisms by which cancer cell invasion is controlled may provide new strategies to impair cancer progression. We investigated the role of the ADP-ribosylation factor (Arf)-like (Arl) protein Arl13b in breast cancer cell migration and invasion in vitro, using breast cancer cell lines and in vivo, using mouse orthotopic models. We show that Arl13b silencing inhibits breast cancer cell migration and invasion in vitro, as well as cancer progression in vivo. We also observed that Arl13b is upregulated in breast cancer cell lines and patient tissue samples. Moreover, we found that Arl13b localizes to focal adhesions (FAs) and interacts with β3-integrin. Upon Arl13b silencing, β3-integrin cell surface levels and FA size are increased and integrin-mediated signaling is inhibited. Therefore, we uncover a role for Arl13b in breast cancer cell migration and invasion and provide a new mechanism for how ARL13B can function as an oncogene, through the modulation of integrin-mediated signaling.

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