scholarly journals Potential Role of MSC/Cancer Cell Fusion and EMT for Breast Cancer Stem Cell Formation

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1432 ◽  
Author(s):  
Ralf Hass ◽  
Juliane von der Ohe ◽  
Hendrik Ungefroren
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Fusion ◽  
Cancer Cell ◽  
Epithelial Mesenchymal Transition ◽  
Cell Formation ◽  
Metastatic Potential ◽  
Cell Types ◽  
Resistance Mechanisms ◽  
Mesenchymal Transition

Solid tumors comprise of maturated cancer cells and self-renewing cancer stem-like cells (CSCs), which are associated with various other nontumorigenic cell populations in the tumor microenvironment. In addition to immune cells, endothelial cells, fibroblasts, and further cell types, mesenchymal stroma/stem-like cells (MSC) represent an important cell population recruited to tumor sites and predominantly interacting with the different cancer cells. Breast cancer models were among the first to reveal distinct properties of CSCs, however, the cellular process(es) through which these cells are generated, maintained, and expanded within neoplastic tissues remains incompletely understood. Here, we discuss several possible scenarios that are not mutually exclusive but may even act synergistically: fusion of cancer cells with MSC to yield hybrid cells and/or the induction of epithelial-mesenchymal transition (EMT) in breast cancer cells by MSC, which can relay signals for retrodifferentiation and eventually, the generation of breast CSCs (BCSCs). In either case, the consequences may be promotion of self-renewal capacity, tumor cell plasticity and heterogeneity, an increase in the cancer cells’ invasive and metastatic potential, and the acquisition of resistance mechanisms towards chemo- or radiotherapy. While specific signaling mechanisms involved in each of these properties remain to be elucidated, the present review article focusses on a potential involvement of cancer cell fusion and EMT in the development of breast cancer stem cells.

scholarly journals Does Direct and Indirect Exposure to Ionising Radiation Influence the Metastatic Potential of Breast Cancer Cells

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 236 ◽  
Author(s):  
Munira A. Kadhim ◽  
Ammar Mayah ◽  
Susan A. Brooks
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Indirect Effects ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Potential ◽  
Ionising Radiation ◽  
Surface Proteins ◽  
In Vivo Models ◽  
Mesenchymal Transition

Ionising radiation (IR) is commonly used for cancer therapy; however, its potential influence on the metastatic ability of surviving cancer cells exposed directly or indirectly to IR remains controversial. Metastasis is a multistep process by which the cancer cells dissociate from the initial site, invade, travel through the blood stream or lymphatic system, and colonise distant sites. This complex process has been reported to require cancer cells to undergo epithelial-mesenchymal transition (EMT) by which the cancer cells convert from an adhesive, epithelial to motile, mesenchymal form and is also associated with changes in glycosylation of cell surface proteins, which may be functionally involved in metastasis. In this paper, we give an overview of metastatic mechanisms and of the fundamentals of cancer-associated glycosylation changes. While not attempting a comprehensive review of this wide and fast moving field, we highlight some of the accumulating evidence from in vitro and in vivo models for increased metastatic potential in cancer cells that survive IR, focusing on angiogenesis, cancer cell motility, invasion, and EMT and glycosylation. We also explore the indirect effects in cells exposed to exosomes released from irradiated cells. The results of such studies need to be interpreted with caution and there remains limited evidence that radiotherapy enhances the metastatic capacity of cancers in a clinical setting and undoubtedly has a very positive clinical benefit. However, there is potential that this therapeutic benefit may ultimately be enhanced through a better understanding of the direct and indirect effects of IR on cancer cell behaviour.

scholarly journals Elaeagnus angustifolia Plant Extract Inhibits Epithelial-Mesenchymal Transition and Induces Apoptosis via HER2 Inactivation and JNK Pathway in HER2-Positive Breast Cancer Cells

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4240 ◽  
Author(s):  
Ayesha Jabeen ◽  
Anju Sharma ◽  
Ishita Gupta ◽  
Hadeel Kheraldine ◽  
Semir Vranic ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Epithelial Mesenchymal Transition ◽  
Elaeagnus Angustifolia ◽  
Her2 Positive ◽  
Mesenchymal Transition ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

Elaeagnus angustifolia (EA) is a medicinal plant used for treating several human diseases in the Middle East. Meanwhile, the outcome of EA extract on HER2-positive breast cancer remains nascent. Thus, we herein investigated the effects of the aqueous EA extract obtained from the flowers of EA on two HER2-positive breast cancer cell lines, SKBR3 and ZR75-1. Our data revealed that EA extract inhibits cell proliferation and deregulates cell-cycle progression of these two cancer cell lines. EA extract also prevents the progression of epithelial-mesenchymal transition (EMT), an important event for cancer invasion and metastasis; this is accompanied by upregulations of E-cadherin and β-catenin, in addition to downregulations of vimentin and fascin, which are major markers of EMT. Thus, EA extract causes a drastic decrease in cell invasion ability of SKBR3 and ZR75-1 cancer cells. Additionally, we found that EA extract inhibits colony formation of both cell lines in comparison with their matched control. The molecular pathway analysis of HER2 and JNK1/2/3 of EA extract exposed cells revealed that it can block HER2 and JNK1/2/3 activities, which could be the major molecular pathway behind these events. Our findings implicate that EA extract may possess chemo-preventive effects against HER2-positive breast cancer via HER2 inactivation and specifically JNK1/2/3 signaling pathways.

scholarly journals ANKRD22 enhances breast cancer cell malignancy by activating the Wnt/β-catenin pathway via modulating NuSAP1 expression

2020 ◽  
Author(s):  
Yange Wu ◽  
Hongxia Liu ◽  
Yufeng Gong ◽  
Bo Zhang ◽  
Wenxiu Chen
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Normal Breast ◽  
Mesenchymal Transition ◽  
New Therapeutic Approaches ◽  
Cell Malignancy

Breast cancer is one of the most prevalent malignancies in women worldwide. Although great progress has been achieved in the diagnosis and treatment of breast cancer, the prognosis of patients with breast cancer is still poor due to distal recurrence and metastasis after surgery. This study demonstrated that the expression level of ankyrin repeat domain 22 (ANKRD22) in human breast cancer tissues was significantly higher than that in normal breast tissues. ANKRD22 knockdown inhibited the proliferation, invasion, and epithelial-mesenchymal transition (EMT) of breast cancer cells. Further research indicated that ANKRD22 regulated the expression of nucleolar and spindle-associated protein 1 (NuSAP1) and then the activation of Wnt/β-catenin signaling pathway. Moreover, overexpression of NuSAP1 reversed the inhibitory effects of ANKRD22 knockdown on the proliferation, invasion, and EMT of breast cancer cells. In summary, this study demonstrated that ANKRD22 enhanced breast cancer cell malignancy by activating the Wnt/β-catenin pathway via modulating NuSAP1 expression, which might shed light on new therapeutic approaches for breast cancer.

scholarly journals The Role of Tumor Microenvironment and Impact of Cancer Stem Cells on Breast Cancer Progression and Growth

2018 ◽  
Vol 0 (0) ◽  
Author(s):  
Nenad Markovic ◽  
Ana Lukovic ◽  
Nebojsa Arsenijevic ◽  
Srdjan Ninkovic ◽  
Biljana Ljujic
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Development ◽  
Inflammatory Cells ◽  
Cell Types ◽  
Cytotoxic Agents ◽  
Molecular Characteristics ◽  
Mesenchymal Transition

Abstract Breast cancer is not only a mass of genetically abnormal tissue in the breast. This is a well-organized system of a complex heterogeneous tissue. Cancer cells produce regulatory signals that stimulate stromal cells to proliferate and migrate; then, stromal elements respond to these signals by releasing components necessary for tumor development that provide structural support, vasculature, and extracellular matrices. Developing tumors can mobilize a variety of cell types from both local and distant niches via secret chemical factors derived from cancer cells themselves or neighboring cells disrupted by growing neoplasm, such as fibroblasts, immune inflammatory cells, and endothelial cells. CSCs are a group of very few cells that are tumorigenic (able to form tumors) and are defined as those cells within a tumor that can self-renew and lead to tumorigenesis. BCSCs represent a small population of cells that have stem cell characteristics and are related to breast cancer. There are different theories about the origin of BCSCs. BCSCs are responsible for breast carcinoma metastasis. Usually, there is a metastatic spread to the bones, and rarely to the lungs and liver. A phenomenon that allows BCSCs to make the transition from epithelial to mesenchymal expression and thus avoid the effect of cytotoxic agents is the epithelial-mesenchymal transition (EMT). During this process, cells change their molecular characteristics in terms of loss of epithelial characteristics taking the mesenchymal phenotype. This process plays a key role in the progression, invasion, and metastasis of breast tumors.

scholarly journals Distinct Ring1b complexes defined by DEAD-box helicases and EMT transcription factors synergistically enhance E-cadherin silencing in breast cancer

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Yawei Wang ◽  
Yingying Sun ◽  
Chao Shang ◽  
Lili Chen ◽  
Hongyu Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcription Factors ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Epigenetic Mechanism ◽  
Regulation Mechanism ◽  
Rna Helicases ◽  
Mesenchymal Transition ◽  
Dead Box ◽  
E Cadherin

AbstractRing1b is a core subunit of polycomb repressive complex 1 (PRC1) and is essential in several high-risk cancers. However, the epigenetic mechanism of Ring1b underlying breast cancer malignancy is poorly understood. In this study, we showed increased expression of Ring1b promoted metastasis by weakening cell–cell adhesions of breast cancer cells. We confirmed that Ring1b could downregulate E-cadherin and contributed to an epigenetic rewiring via PRC1-dependent function by forming distinct complexes with DEAD-box RNA helicases (DDXs) or epithelial-mesenchymal transition transcription factors (EMT TFs) on site-specific loci of E-cadherin promoter. DDXs-Ring1b complexes moderately inhibited E-cadherin, which resulted in an early hybrid EMT state of epithelial cells, and EMT TFs-Ring1b complexes cooperated with DDXs-Ring1b complexes to further repress E-cadherin in mesenchymal-like cancer cells. Clinically, high expression of Ring1b with DDXs or EMT TFs predicted low levels of E-cadherin, metastatic behavior, and poor prognosis. These findings provide an epigenetic regulation mechanism of Ring1b complexes in E-cadherin expression. Ring1b complexes may be potential therapeutic targets and biomarkers for diagnosis and prognosis in invasion breast cancer.

scholarly journals Involvement of the ERK/HIF-1α/EMT Pathway in XCL1-Induced Migration of MDA-MB-231 and SK-BR-3 Breast Cancer Cells

2020 ◽  
Vol 22 (1) ◽  
pp. 89
Author(s):  
Ha Thi Thu Do ◽  
Jungsook Cho
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Chemokine Receptor ◽  
Intracellular Signaling ◽  
Breast Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Mitogen Activated Protein Kinase ◽  
Mesenchymal Transition

Chemokine–receptor interactions play multiple roles in cancer progression. It was reported that the overexpression of X-C motif chemokine receptor 1 (XCR1), a specific receptor for chemokine X-C motif chemokine ligand 1 (XCL1), stimulates the migration of MDA-MB-231 triple-negative breast cancer cells. However, the exact mechanisms of this process remain to be elucidated. Our study found that XCL1 treatment markedly enhanced MDA-MB-231 cell migration. Additionally, XCL1 treatment enhanced epithelial–mesenchymal transition (EMT) of MDA-MB-231 cells via E-cadherin downregulation and upregulation of N-cadherin and vimentin as well as increases in β-catenin nucleus translocation. Furthermore, XCL1 enhanced the expression of hypoxia-inducible factor-1α (HIF-1α) and phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. Notably, the effects of XCL1 on cell migration and intracellular signaling were negated by knockdown of XCR1 using siRNA, confirming XCR1-mediated actions. Treating MDA-MB-231 cells with U0126, a specific mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor, blocked XCL1-induced HIF-1α accumulation and cell migration. The effect of XCL1 on cell migration was also evaluated in ER-/HER2+ SK-BR-3 cells. XCL1 also promoted cell migration, EMT induction, HIF-1α accumulation, and ERK phosphorylation in SK-BR-3 cells. While XCL1 did not exhibit any significant impact on the matrix metalloproteinase (MMP)-2 and -9 expressions in MDA-MB-231 cells, it increased the expression of these enzymes in SK-BR-3 cells. Collectively, our results demonstrate that activation of the ERK/HIF-1α/EMT pathway is involved in the XCL1-induced migration of both MDA-MB-231 and SK-BR-3 breast cancer cells. Based on our findings, the XCL1–XCR1 interaction and its associated signaling molecules may serve as specific targets for the prevention of breast cancer cell migration and metastasis.

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