scholarly journals Harmine inhibits breast cancer cell migration and invasion by inducing the degradation of Twist1

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0247652
Author(s):  
Ebtesam Nafie ◽  
Jade Lolarga ◽  
Brandon Lam ◽  
Jonathan Guo ◽  
Elnaz Abdollahzadeh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcription Factor ◽  
Cell Migration ◽  
Metastatic Breast Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Metastatic Breast ◽  
Migration And Invasion ◽  
Cancer Cell Migration

Breast cancer is the leading cause of cancer-related deaths in the United States. The majority of deaths (90%) in breast cancer patients is caused by invasion and metastasis–two features related to the epithelial-to-mesenchymal transition (EMT). Twist1 is a key transcription factor that promotes the EMT, which leads to cell migration, invasion, cancer metastasis, and therapeutic resistance. Harmine is a beta-carboline alkaloid found in a variety of plants and was recently shown to be able to induce degradation of Twist Family BHLH Transcription Factor 1 (Twist1) in non-small cell lung cancer cells (NSCLC). In this study, we show that harmine can inhibit migration and invasion of both human and mouse breast cancer cells in a dose-dependent manner. Further study shows that this inhibition is most likely achieved by inducing a proteasome-dependent Twist1 degradation. At the concentrations tested, harmine did not affect the viability of cells significantly, suggesting that its inhibition of cancer cell migration and invasion is largely independent of its cytotoxicity, but due to its ability to affect regulators of EMT such as Twist1. This result may facilitate the development of strategies that target Twist1 to treat metastatic breast cancer, as Twist1 is expressed at a high level in metastatic breast cancer cells but not in normal cells.

A fluorescence nanoprobe for detecting the effect of different oxygen and nutrient conditions on breast cancer cells migration and invasion

2021 ◽  
Author(s):  
Ping Zhou ◽  
Bo Liu ◽  
Mingming Luan ◽  
Na Li ◽  
Bo Tang
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Tumor Metastasis ◽  
Migration And Invasion ◽  
Cancer Cell Migration ◽  
Fluorescence Nanoprobe

Cancer cell migration and invasion are initial steps for tumor metastasis that increases patient mortality. Tumor microenvironment is characterized by hypoxic and low nutrient-containing. Previous studies have suggested that hypoxia...

ECM1 secreted by HER2-overexpressing breast cancer cells promotes formation of a vascular niche accelerating cancer cell migration and invasion

2020 ◽  
Vol 100 (7) ◽  
pp. 928-944
Author(s):  
Sophie Sarah Steinhaeuser ◽  
Erika Morera ◽  
Zuzana Budkova ◽  
Alexander Schepsky ◽  
Qiong Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Cancer Cell Migration ◽  
Cell Migration And Invasion ◽  
Vascular Niche

scholarly journals Weakly migratory metastatic breast cancer cells activate fibroblasts via microvesicle-Tg2 to facilitate dissemination and metastasis

2021 ◽  
Author(s):  
Samantha C Schwager ◽  
Lauren A Hapach ◽  
Caroline M Carlson ◽  
Jenna A Mosier ◽  
Tanner J McArdle ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Primary Tumor ◽  
Breast Cancer Cells ◽  
Tissue Transglutaminase ◽  
Metastatic Breast ◽  
Cancer Cell Migration ◽  
Migratory Cells

Cancer cell migration is highly heterogeneous, and the migratory capability of cancer cells is thought to be an indicator of metastatic potential. It is becoming clear that a cancer cell does not have to be inherently migratory to metastasize, with weakly migratory cancer cells often found to be highly metastatic. However, the mechanism through which weakly migratory cells escape from the primary tumor remains unclear. Here, utilizing phenotypically sorted highly and weakly migratory breast cancer cells, we demonstrate that weakly migratory metastatic cells disseminate from the primary tumor via communication with stromal cells. While highly migratory cells are capable of single cell migration, weakly migratory cells rely on cell-cell signaling with fibroblasts to escape the primary tumor. Weakly migratory cells release microvesicles rich in tissue transglutaminase 2 (Tg2) which activate fibroblasts and lead weakly migratory cancer cell migration in vitro. These microvesicles also induce tumor stiffening and fibroblast activation in vivo and enhance the metastasis of weakly migratory cells. Our results identify microvesicles and Tg2 as potential therapeutic targets for metastasis and reveal a novel aspect of the metastatic cascade in which weakly migratory cells release microvesicles which activate fibroblasts to enhance cancer cell dissemination.

scholarly journals RUNX/CBFβ transcription factor complexes promote the phenotypic plasticity of metastatic breast cancer cells

2019 ◽  
Author(s):  
Ran Ran ◽  
Hannah Harrison ◽  
Nur Syamimi Ariffin ◽  
Rahna Ayub ◽  
Henry J Pegg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcription Factor ◽  
Metastatic Breast Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Metastatic Cancer ◽  
Metastatic Breast ◽  
Mesenchymal Transition

AbstractEpithelial to mesenchymal transition (EMT) is a dynamic process that drives cancer cell plasticity and is thought to play a major role in metastasis. Here we show that the plasticity of metastatic breast cancer cells can be promoted by the activity of the RUNX transcription factors. We demonstrate that the RUNX co-regulator CBFβ is essential to maintain the mesenchymal phenotype of triple-negative breast cancer cells and that CBFβ-depleted cells undergo a mesenchymal to epithelial transition (MET) and re-organise into acini-like structures, reminiscent of those formed by epithelial breast cells. We subsequently show, using an inducible CBFβ system, that the MET can be reversed, thus demonstrating the plasticity of RUNX/CBFβ-mediated EMT. Moreover, the MET can be reversed by expression of the EMT transcription factor Slug whose expression is dependent on CBFβ, RUNX1 and RUNX2. Finally, we demonstrate that loss of CBFβ inhibits the ability of metastatic breast cancer cells to invade bone cell cultures and suppresses their ability to form bone metastasesin vivo. Together our findings demonstrate that the RUNX/CBFβ complexes can determine the plasticity of the metastatic cancer cell phenotypes, suggesting that their regulation in different micro-environments may play a key role in the establishment of metastatic tumours.

scholarly journals Ephexin4 and EphA2 mediate cell migration through a RhoG-dependent mechanism

2010 ◽  
Vol 190 (3) ◽  
pp. 461-477 ◽  
Author(s):  
Nao Hiramoto-Yamaki ◽  
Shingo Takeuchi ◽  
Shuhei Ueda ◽  
Kohei Harada ◽  
Satoshi Fujimoto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cell Motility ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Cancer Cell Migration ◽  
Breast Cancer Cell Migration

EphA2, a member of the Eph receptor family, is frequently overexpressed in a variety of human cancers, including breast cancers, and promotes cancer cell motility and invasion independently of its ligand ephrin stimulation. In this study, we identify Ephexin4 as a guanine nucleotide exchange factor (GEF) for RhoG that interacts with EphA2 in breast cancer cells, and knockdown and rescue experiments show that Ephexin4 acts downstream of EphA2 to promote ligand-independent breast cancer cell migration and invasion toward epidermal growth factor through activation of RhoG. The activation of RhoG recruits its effector ELMO2 and a Rac GEF Dock4 to form a complex with EphA2 at the tips of cortactin-rich protrusions in migrating breast cancer cells. In addition, the Dock4-mediated Rac activation is required for breast cancer cell migration. Our findings reveal a novel link between EphA2 and Rac activation that contributes to the cell motility and invasiveness of breast cancer cells.

scholarly journals Progesterone promotes focal adhesion formation and migration in breast cancer cells through induction of protease-activated receptor-1

2012 ◽  
Vol 214 (2) ◽  
pp. 165-175 ◽  
Author(s):  
Jorge Diaz ◽  
Evelyn Aranda ◽  
Soledad Henriquez ◽  
Marisol Quezada ◽  
Estefanía Espinoza ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Focal Adhesion ◽  
Breast Cancer Cells ◽  
Fiber Formation ◽  
Coagulation Cascade ◽  
Cancer Cell Migration

Progesterone and progestins have been demonstrated to enhance breast cancer cell migration, although the mechanisms are still not fully understood. The protease-activated receptors (PARs) are a family of membrane receptors that are activated by serine proteases in the blood coagulation cascade. PAR1 (F2R) has been reported to be involved in cancer cell migration and overexpressed in breast cancer. We herein demonstrate that PAR1 mRNA and protein are upregulated by progesterone treatment of the breast cancer cell lines ZR-75 and T47D. This regulation is dependent on the progesterone receptor (PR) but does not require PR phosphorylation at serine 294 or the PR proline-rich region mPRO. The increase in PAR1 mRNA was transient, being present at 3 h and returning to basal levels at 18 h. The addition of a PAR1-activating peptide (aPAR1) to cells treated with progesterone resulted in an increase in focal adhesion (FA) formation as measured by the cellular levels of phosphorylated FA kinase. The combined but not individual treatment of progesterone and aPAR1 also markedly increased stress fiber formation and the migratory capacity of breast cancer cells. In agreement with in vitro findings, data mining from the Oncomine platform revealed that PAR1 expression was significantly upregulated in PR-positive breast tumors. Our observation that PAR1 expression and signal transduction are modulated by progesterone provides new insight into how the progestin component in hormone therapies increases the risk of breast cancer in postmenopausal women.

scholarly journals ATP Inhibits Breast Cancer Migration and Bone Metastasis through Down-Regulation of CXCR4 and Purinergic Receptor P2Y11

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4293
Author(s):  
Xiaowen Liu ◽  
Manuel A. Riquelme ◽  
Yi Tian ◽  
Dezhi Zhao ◽  
Francisca M. Acosta ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Bone Metastasis ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Cxcr4 Expression ◽  
Dependent Manner ◽  
Cancer Cell Migration ◽  
Dose Dependent

ATP released by bone osteocytes is shown to activate purinergic signaling and inhibit the metastasis of breast cancer cells into the bone. However, the underlying molecular mechanism is not well understood. Here, we demonstrate the important roles of the CXCR4 and P2Y11 purinergic receptors in mediating the inhibitory effect of ATP on breast cancer cell migration and bone metastasis. Wound-healing and transwell migration assays showed that non-hydrolysable ATP analogue, ATPγS, inhibited migration of bone-tropic human breast cancer cells in a dose-dependent manner. BzATP, an agonist for P2X7 and an inducer for P2Y11 internalization, had a similar dose-dependent inhibition on cell migration. Both ATPγS and BzATP suppressed the expression of CXCR4, a chemokine receptor known to promote breast cancer bone metastasis, and knocking down CXCR4 expression by siRNA attenuated the inhibitory effect of ATPγS on cancer cell migration. While a P2X7 antagonist A804598 had no effect on the impact of ATPγS on cell migration, antagonizing P2Y11 by NF157 ablated the effect of ATPγS. Moreover, the reduction in P2Y11 expression by siRNA decreased cancer cell migration and abolished the impact of ATPγS on cell migration and CXCR4 expression. Similar to the effect of ATPγS on cell migration, antagonizing P2Y11 inhibited bone-tropic breast cancer cell migration in a dose-dependent manner. An in vivo study using an intratibial bone metastatic model showed that ATPγS inhibited breast cancer growth in the bone. Taken together, these results suggest that ATP inhibits bone-tropic breast cancer cells by down-regulating the P2Y11 purinergic receptor and the down-regulation of CXCR4 expression.

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