Opposite response to hypoxia by breast cancer cells between cell proliferation and cell migration: A clue from microRNA expression profile

Objectives: In this study, we assess the possible influence of soybean isoflavone (genistein) and other flavonoids (quercetin and catechin) on breast cancer chemoprevention. We design in-vitro and in-vivo experiments to analyze the effect of genistein, quercetin and catechin on cell proliferation, cell migration, and angiogenesis of breast cancer cells. Methods: In cell proliferation experiment, MCF-7 cells, SKBR-3 cells, and HUVEC cells were treated with genistein and other flavonoids (catechin and/or quercetin) for 48[Formula: see text]h to assess the influence on cell growth of normal and breast cancer cells. In cell motility test, we analyze the effect of isoflavone and flavonoids on migration ability of MCF-7 cells by 16[Formula: see text]h and SKBR-3 cells by 24[Formula: see text]h in two different concentrations (1.25[Formula: see text][Formula: see text]g/ml and 2.5[Formula: see text][Formula: see text]g/ml). In the in-vivo experiment, SKBR-3 cells mixed with PBS and catechin, respectively, were injected subcutaneously into nude mice, then we investigated the effect of catechin on cell growth by observing subcutaneous tumor size changes after 15 days. Results: The results suggest that genistein and quercetin can significantly inhibit proliferation of breast cancer cells, and their inhibitory effects are independent of estrogen receptor. In cell motility tests, all of the three phytochemicals were effective in the inhibition of cell migration on two breast cancer cell lines, except for quercetin on cell migration of SKBR-3 cell line. In the in-vitro experiment, catechin showed stimulatory effect on cell proliferation of HUVEC cell line, which may consider positive effect on angiogenesis, rather than inhibitory effect. However, in the in-vivo experiment, it showed no significant change in tumor size between the groups of with and without catechin treatment. Conclusions: According to our study, the results suggest that isoflavone and flavonoids tend to inhibit cell growth and metastasis of breast cancer cells. Our in-vivo experiment does not reach a significant result, and it may be due to lower catechin concentration. Under in-vivo environment, we should also consider the possible metabolic forms of catechin that cause different result from the in-vitro study.

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miR-448 inhibits the epithelial-mesenchymal transition in breast cancer cells by directly targeting the E-cadherin repressor ZEB1/2

Experimental Biology and Medicine ◽

10.1177/1535370218754848 ◽

2018 ◽

Vol 243 (5) ◽

pp. 473-480 ◽

Cited By ~ 17

Author(s):

Peng Ma ◽

Kan Ni ◽

Jing Ke ◽

Wenyi Zhang ◽

Ying Feng ◽

...

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Cell Migration ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Migration And Invasion ◽

Rt Pcr ◽

Mesenchymal Transition ◽

E Cadherin

Recently, accumulating evidence provides that dysregulation of microRNAs (miRNAs) is considered to play vital roles in tumor progression. Based on microRNA arrays, we found that microRNA-448 (miR-448) was significantly downregulated in breast cancer tissue specimens. In our study, we were in an effort to clarify the function, the direct target gene, and the molecular mechanisms of miR-448 in breast cancer. By quantitative RT–PCR, we analyzed the expression of miR-448 in 16 patients with BC. Overexpression of miR-448 was established by transfecting miR-448-mimics into MDA-MB-231 and MCF-7 cells, methyl thiazolyl- tetrazolium and colony formation assays were performed to evaluate its effects on cell proliferation. We also performed cell migration and invasion assays in breast cells overexpressing miRNA-448. All the results indicated that overexpression of miR-448 in breast cancer cells markedly suppressed cell proliferation, migration, and invasion. Through the quantitative RT–PCR and Western Blots, we also evaluated epithelial–mesenchymal transition. We found that overexpression of miR-448 also downregulated the expression of vimentin, a well-known mesenchymal marker. Meanwhile, the epithelial marker E-cadherin was unregulated, suggesting that miR-448 inhibited epithelial–mesenchymal transition . Bioinformatics assay coupled with Western Blot and luciferase assays revealed that miR-448 directly binds to the 3′UTR of E-cadherin repressor ZEB1/2, resulting in suppression of epithelial–mesenchymal transition in breast cancer cells. Impact statement In our study, we revealed that miR-448 played a vital role in breast cancer development and we also uncovered the mechanisms of it. Following is the short description of the main findings: miR-448 is downregulated in BC. miR-448 regulates cell proliferation, migration, and invasion in BC. miR-448 specifically regulates ZEB1/2 through binding to the 3′UTR in BC cells. miR-448 inhibits cell migration, invasion, and EMT by targeting to the 3′UTR of ZEB1/2.

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Docking Protein 2 Inhibits Proliferation, Migration and Invasion of Breast Cancer Cells via the Ras/Extracellular Regulated Protein Kinases Pathway

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2020.2319 ◽

2020 ◽

Vol 10 (5) ◽

pp. 690-697

Author(s):

Yongmei Zhang ◽

Huayi Zhang ◽

Gang Guo ◽

Xiping Zhang

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Cell Migration ◽

Western Blot ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Migration And Invasion ◽

Erk Pathway ◽

Related Proteins ◽

Docking Protein

Background: This study was designed to investigate the effects of Downstream of Tyrosine Kinase 2, Docking Protein 2 (DOK2) on breast cancer cells, and its potential mechanism in disease pathogenesis. Methods: The expression of DOK2 in human breast cancer cell lines and mammary epithelial cells were assessed by RT-qPCR and Western blot assay. CCK8 was used to evaluate cell proliferation, wound healing and transwell were used to detect cell migration and invasion. Furthermore, Western blot was used to detect the expression of migration-related proteins, MMP2, MMP9 and Ras/ERK pathway-related proteins. Results: The expression level of DOK2 was significantly lower in breast cancer MCF7 and MDA-MB-231 cells compared with the normal breast cancer cell line MCF10A. To further investigate the function of DOK2, the overexpressed plasmid of DOK2 was transfected into MCF7 and MDA-MB-231 cells, the results revealed that DOK2 markedly inhibited cell proliferation, cell migration and invasion via inhibiting the Ras/ERK pathway. Conclusions: Collectively, the data demonstrated that DOK2 could directly inhibits proliferation, migration and invasion of breast cancers via inhibiting the Ras/ERK pathway.

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Calreticulin Overexpression Suppresses Cell Proliferation and Enhances Apoptosis on Human MCF-7 Breast Cancer Cells

International Journal of Advances in Chemical Engineering and Biological Sciences ◽

10.15242/ijacebs.c1213012 ◽

2014 ◽

Vol 1 (1) ◽

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Mcf 7

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Matrix degradation and cell proliferation are coupled to promote invasion and escape from an engineered human breast microtumor

Integrative Biology ◽

10.1093/intbio/zyaa026 ◽

2021 ◽

Vol 13 (1) ◽

pp. 17-29

Author(s):

Emann M Rabie ◽

Sherry X Zhang ◽

Andreas P Kourouklis ◽

A Nihan Kilinc ◽

Allison K Simi ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cell Proliferation ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Type I ◽

Matrix Degradation ◽

Human Breast ◽

Rate Of Invasion

Abstract Metastasis, the leading cause of mortality in cancer patients, depends upon the ability of cancer cells to invade into the extracellular matrix that surrounds the primary tumor and to escape into the vasculature. To investigate the features of the microenvironment that regulate invasion and escape, we generated solid microtumors of MDA-MB-231 human breast carcinoma cells within gels of type I collagen. The microtumors were formed at defined distances adjacent to an empty cavity, which served as an artificial vessel into which the constituent tumor cells could escape. To define the relative contributions of matrix degradation and cell proliferation on invasion and escape, we used pharmacological approaches to block the activity of matrix metalloproteinases (MMPs) or to arrest the cell cycle. We found that blocking MMP activity prevents both invasion and escape of the breast cancer cells. Surprisingly, blocking proliferation increases the rate of invasion but has no effect on that of escape. We found that arresting the cell cycle increases the expression of MMPs, consistent with the increased rate of invasion. To gain additional insight into the role of cell proliferation in the invasion process, we generated microtumors from cells that express the fluorescent ubiquitination-based cell cycle indicator. We found that the cells that initiate invasions are preferentially quiescent, whereas cell proliferation is associated with the extension of invasions. These data suggest that matrix degradation and cell proliferation are coupled during the invasion and escape of human breast cancer cells and highlight the critical role of matrix proteolysis in governing tumor phenotype.

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Highly expressed SLCO1B3 inhibits the occurrence and development of breast cancer and can be used as a clinical indicator of prognosis

Scientific Reports ◽

10.1038/s41598-020-80152-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Tiantian Tang ◽

Guiying Wang ◽

Sihua Liu ◽

Zhaoxue Zhang ◽

Chen Liu ◽

...

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Breast Cancer Cells ◽

Migration And Invasion ◽

Breast Cancer Cell Lines

AbstractThe role of organic anion transporting polypeptide 1B3 (SLCO1B3) in breast cancer is still controversial. The clinical immunohistochemical results showed that a greater proportion of patients with negative lymph nodes, AJCC stage I, and histological grade 1 (P < 0.05) was positively correlated with stronger expression of SLCO1B3, and DFS and OS were also increased significantly in these patients (P = 0.041, P = 0.001). Further subgroup analysis showed that DFS and OS were significantly enhanced with the increased expression of SLCO1B3 in the ER positive subgroup. The cellular function assay showed that the ability of cell proliferation, migration and invasion was significantly enhanced after knockdown of SLCO1B3 expression in breast cancer cell lines. In contrast, the ability of cell proliferation, migration and invasion was significantly reduced after overexpress the SLCO1B3 in breast cancer cell lines (P < 0.05). Overexpression or knockdown of SLCO1B3 had no effect on the apoptotic ability of breast cancer cells. High level of SLCO1B3 expression can inhibit the proliferation, invasion and migration of breast cancer cells, leading to better prognosis of patients. The role of SLCO1B3 in breast cancer may be related to estrogen. SLCO1B3 will become a potential biomarker for breast cancer diagnosis and prognosis assessment.

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

International Journal of Molecular Sciences ◽

10.3390/ijms22010089 ◽

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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ILF3-AS1 promotes cell proliferation and inhibits cell apoptosis of breast cancer by binding with miR-4429 to upregulate RAB14

Human & Experimental Toxicology ◽

10.1177/0960327121989422 ◽

2021 ◽

pp. 096032712198942

Author(s):

Xiaoxue Zhang ◽

Xianxin Xie ◽

Kuiran Gao ◽

Xiaoming Wu ◽

Yanwei Chen ◽

...

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Breast Cancer Cell ◽

Cell Apoptosis ◽

Breast Cancer Cells ◽

Migration And Invasion ◽

Cancer Cell Proliferation ◽

Breast Cancer Cell Proliferation ◽

Cancer Tissues

As one of the leading causes of cancer-related deaths among women, breast cancer accounts for a 30% increase of incidence worldwide since 1970s. Recently, increasing studies have revealed that the long non-coding RNA ILF3-AS1 is involved in the progression of various cancers. Nevertheless, the role of ILF3-AS1 in breast cancer remains largely unknown. In the present study, we found that ILF3-AS1 was highly expressed in breast cancer tissues and cells. ILF3-AS1 silencing inhibited breast cancer cell proliferation, migration and invasion, and promoted cell apoptosis. ILF3-AS1 bound with miR-4429 in breast cancer cells. Moreover, RAB14 was a downstream target of miR-4429, and miR-4429 expression was negatively correlated with RAB14 or ILF3-AS1 expression in breast cancer tissues. The result of rescue experiments demonstrated that overexpression of RAB14 can reverse the inhibitory effect of ILF3-AS1 knockdown on breast cancer cell proliferation, migration and invasion. Overall, ILF3-AS1 promotes the malignant phenotypes of breast cancer cells by interacting with miR-4429 to regulate RAB14, which might offer a new insight into the underlying mechanism of breast cancer.

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