scholarly journals Loss of PTPN12 Stimulates Progression of ErbB2-Dependent Breast Cancer by Enhancing Cell Survival, Migration, and Epithelial-to-Mesenchymal Transition

2015 ◽  
Vol 35 (23) ◽  
pp. 4069-4082 ◽  
Author(s):  
Juan Li ◽  
Dominique Davidson ◽  
Cleiton Martins Souza ◽  
Ming-Chao Zhong ◽  
Ning Wu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mouse Model ◽  
Cell Survival ◽  
Tyrosine Phosphorylation ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Breast Cancer Progression ◽  
Mesenchymal Transition

PTPN12 is a cytoplasmic protein tyrosine phosphatase (PTP) reported to be a tumor suppressor in breast cancer, through its capacity to dephosphorylate oncogenic receptor protein tyrosine kinases (PTKs), such as ErbB2. However, the precise molecular and cellular impact of PTPN12 deficiency in breast cancer progression remains to be fully clarified. Here, we addressed this issue by examining the effect of PTPN12 deficiency on breast cancer progressionin vivo, in a mouse model of ErbB2-dependent breast cancer using a conditional PTPN12-deficient mouse. Our studies showed that lack of PTPN12 in breast epithelial cells accelerated breast cancer development and lung metastasesin vivo. PTPN12-deficient breast cancer cells displayed enhanced tyrosine phosphorylation of the adaptor Cas, the adaptor paxillin, and the kinase Pyk2. They exhibited no detectable increase in ErbB2 tyrosine phosphorylation. PTPN12-deficient cells were more resistant to anoikis and had augmented migratory and invasive properties. Enhanced migration was corrected by inhibiting Pyk2. PTPN12-deficient breast cancer cells also acquired partial features of epithelial-to-mesenchymal transition (EMT), a feature of more aggressive forms of breast cancer. Hence, loss of PTPN12 promoted tumor progression in a mouse model of breast cancer, supporting the notion that PTPN12 is a tumor suppressor in human breast cancer. This function was related to the ability of PTPN12 to suppress cell survival, migration, invasiveness, and EMT and to inhibit tyrosine phosphorylation of Cas, Pyk2, and paxillin. These findings enhance our understanding of the role and mechanism of action of PTPN12 in the control of breast cancer progression.

LncRNA NEAT1 accelerates breast cancer progression through regulating miR-410-3p/ CCND1 axis

2020 ◽  
Vol 29 (2) ◽  
pp. 277-290
Author(s):  
Xuan Liu ◽  
Weirong Yao ◽  
Haiwei Xiong ◽  
Qiang Li ◽  
Yingliang Li
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Breast Cancer Progression ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Cancer Tissues

BACKGROUND: Breast cancer is the most common malignant tumor and usually occurs in women. Studies have shown that lncRNA nuclear enriched abundant transcript 1 (NEAT1) contributes to breast cancer progression. This study intends to further investigate the molecular mechanism of NEAT1 in breast cancer. METHODS: The expression levels of NEAT1, miR-410-3p and Cyclin D1 (CCND1) were detected by quantitative real-time PCR (qRT-PCR) in breast cancer tissues and cells. Kaplan-Meier analysis and the log-rank test were performed to determine the relationship between NEAT1 and overall survival. Cell Counting Kit-8 (CCK-8) assay analyzed cell proliferation. Transwell assay was performed to examine cell migration and invasion. The protein levels of CCND1 and epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin, N-cadherin and Vimentin) were measured by western blot. The target relationship was predicted by bioinformatics analysis, and confirmed by luciferase reporter assay and RNA Immunoprecipitation (RIP) assay. Xenograft analysis was used to evaluate the tumor growth in vivo. RESULTS: NEAT1 and CCND1 were upregulated, while miR-410-3p was down-regulated in breast cancer tissues and cells. Higher NEAT1 expression level was associated with lower survival rate of breast cancer patients. Knockdown of miR-410-3p restored silenced NEAT1-mediated the inhibition of on proliferation, migration, invasion and EMT of breast cancer cells. In addition, NEAT1 regulated CCND1 expression by sponging miR-410-3p in breast cancer cells. NEAT1 knockdown blocked the tumor growth in vivo. CONCLUSION: NEAT1 induced breast cancer progression by regulating the miR-410-3p/CCND1 axis, indicating that NEAT1 may be a potential therapeutic target in breast cancer.

scholarly journals Morphine Promotes Tumor Angiogenesis and Increases Breast Cancer Progression

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Sabrina Bimonte ◽  
Antonio Barbieri ◽  
Domenica Rea ◽  
Giuseppe Palma ◽  
Antonio Luciano ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Growth ◽  
Mouse Model ◽  
Cancer Progression ◽  
Breast Cancer Progression ◽  
Cancer Cell Growth ◽  
Patients With Cancer ◽  
Human Breast Carcinoma Cells

Morphine is considered a highly potent analgesic agent used to relieve suffering of patients with cancer. Severalin vitroandin vivostudies showed that morphine also modulates angiogenesis and regulates tumour cell growth. Unfortunately, the results obtained by these studies are still contradictory. In order to better dissect the role of morphine in cancer cell growth and angiogenesis we performedin vitrostudies on ER-negative human breast carcinoma cells, MDA.MB231 andin vivostudies on heterotopic mouse model of human triple negative breast cancer, TNBC. We demonstrated that morphinein vitroenhanced the proliferation and inhibited the apoptosis of MDA.MB231 cells.In vivostudies performed on xenograft mouse model of TNBC revealed that tumours of mice treated with morphine were larger than those observed in other groups. Moreover, morphine was able to enhance the neoangiogenesis. Our data showed that morphine at clinical relevant doses promotes angiogenesis and increases breast cancer progression.

scholarly journals Arctigenin Attenuates Breast Cancer Progression through Decreasing GM-CSF/TSLP/STAT3/β-Catenin Signaling

2020 ◽  
Vol 21 (17) ◽  
pp. 6357
Author(s):  
Hui Shi ◽  
Luping Zhao ◽  
Xinlin Guo ◽  
Runping Fang ◽  
Hui Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Nuclear Translocation ◽  
Breast Cancer Progression ◽  
Gm Csf ◽  
Stat3 Phosphorylation

Invasive breast cancer is highly regulated by tumor-derived cytokines in tumor microenvironment. The development of drugs that specifically target cytokines are promising in breast cancer treatment. In this study, we reported that arctigenin, a bioactive compound from Arctium lappa L., could decrease tumor-promoting cytokines GM-CSF, MMP-3, MMP-9 and TSLP in breast cancer cells. Arctigenin not only inhibited the proliferation, but also the invasion and stemness of breast cancer cells via decreasing GM-CSF and TSLP. Mechanistically, arctigenin decreased the promoter activities of GM-CSF and TSLP via reducing the nuclear translocation of NF-κB p65 which is crucial for the transcription of GM-CSF and TSLP. Furthermore, arctigenin-induced depletion of GM-CSF and TSLP inhibited STAT3 phosphorylation and β-catenin signaling resulting in decreased proliferation, invasion and stemness of breast cancer cells in vitro and in vivo. Our findings provide new insights into the mechanism by which tumor-promoting cytokines regulate breast cancer progression and suggest that arctigenin is a promising candidate for cytokine-targeted breast cancer therapy.

scholarly journals MicroRNA-374b inhibits breast cancer progression through regulating CCND1 and TGFA genes

2021 ◽  
Author(s):  
Yan Liu ◽  
Ai Zhang ◽  
Ping-Ping Bao ◽  
Li Lin ◽  
Yina Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Breast Cancer Progression ◽  
Breast Cancer Cell Lines ◽  
Malignant Behavior

Abstract Emerging evidence indicates that microRNAs (miRNAs) play a critical role in breast cancer development. We recently reported that a higher expression of miR-374b in tumor tissues was associated with a better disease-free survival of triple-negative breast cancer (TNBC). However, the functional significance and molecular mechanisms underlying the role of miR-374b in breast cancer are largely unknown. In this current study, we evaluated the biological functions and potential mechanisms of miR-374b in both TNBC and non-TNBC. We found that miR-374b was significantly downregulated in breast cancer tissues, compared to adjacent tissues. MiR-374b levels were also lower in breast cancer cell lines, as compared to breast epithelial cells. In vitro and in vivo studies demonstrated that miR-374b modulates the malignant behavior of breast cancer cells, such as cell proliferation in 2D and 3D, cell invasion ability, colony forming ability, and tumor growth in mice. By using bioinformatics tools, we predicted that miR-374b plays a role in breast cancer cells through negatively regulating cyclin D1 (CCND1) and transforming growth factor alpha (TGFA). We further confirmed that CCND1 and TGFA contribute to the malignant behavior of breast cancer cells in vitro and in vivo. Our rescue experiments showed that overexpressing CCND1 or TGFA reverses the phenotypes caused by miR-374b overexpression. Taken together, our studies suggest that miR-374b modulates malignant behavior of breast cancer cells by negatively regulating CCND1 and TGFA genes. The newly identified miR-374b-mediated CCND1 and TGFA gene silencing may facilitate a better understanding of the molecular mechanisms of breast cancer progression.

scholarly journals Silencing of KIF3B Suppresses Breast Cancer Progression by Regulating EMT and Wnt/β-Catenin Signaling

2021 ◽  
Vol 10 ◽  
Author(s):  
Chengqin Wang ◽  
Runze Zhang ◽  
Xiao Wang ◽  
Yan Zheng ◽  
Huiqing Jia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Breast Cancer Progression ◽  
Migration And Invasion ◽  
Breast Cancer Cell Lines ◽  
Mesenchymal Transition ◽  
Cancer Tissues

Breast cancer is the most common malignant tumors in women. Kinesin family member 3B (KIF3B) is a critical regulator in mitotic progression. The objective of this study was to explore the expression, regulation, and mechanism of KIF3B in 103 cases of breast cancer tissues, 35 metastatic lymph nodes and breast cancer cell lines, including MDA-MB-231, MDA-MB-453, T47D, and MCF-7. The results showed that KIF3B expression was up-regulated in breast cancer tissues and cell lines, and the expression level was correlated with tumor recurrence and lymph node metastasis, while knockdown of KIF3B suppressed cell proliferation, migration, and invasion both in vivo and in vitro. In addition, UALCAN analysis showed that KIF3B expression in breast cancer is increased, and the high expression of KIF3B in breast cancer is associated with poor prognosis. Furthermore, we found that silencing of KIF3B decreased the expression of Dvl2, phospho-GSK-3β, total and nucleus β-catenin, then subsequent down-regulation of Wnt/β-catenin signaling target genes such as CyclinD1, C-myc, MMP-2, MMP-7 and MMP-9 in breast cancer cells. In addition, KIF3B depletion inhibited epithelial mesenchymal transition (EMT) in breast cancer cells. Taken together, our results revealed that KIF3B is up-regulated in breast cancer which is potentially involved in breast cancer progression and metastasis. Silencing KIF3B might suppress the Wnt/β-catenin signaling pathway and EMT in breast cancer cells.

scholarly journals Epithelial to Mesenchymal Transition Promotes Breast Cancer Progression via a Fibronectin-dependent STAT3 Signaling Pathway

2013 ◽  
Vol 288 (25) ◽  
pp. 17954-17967 ◽  
Author(s):  
Nikolas Balanis ◽  
Michael K. Wendt ◽  
Barbara J. Schiemann ◽  
Zhenghe Wang ◽  
William P. Schiemann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Breast Cancer Progression ◽  
Mesenchymal Transition ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

scholarly journals Long Non-Coding RNA LINC00467 Correlates to Poor Prognosis and Aggressiveness of Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Ying Zhang ◽  
Yi Sun ◽  
Lin Ding ◽  
Wenjing Shi ◽  
Keshuo Ding ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Direct Interaction ◽  
Potential Candidate ◽  
Poor Overall Survival ◽  
Mesenchymal Transition ◽  
Cancer Tissues

Breast cancer remains the leading cause of female cancer-related mortalities worldwide. Long non-coding RNAs (LncRNAs) have been increasingly reported to play pivotal roles in tumorigenesis and cancer progression. Herein, we focused on LINC00467, which has never been studied in breast cancer. Silence of LINC00467 suppressed proliferation, migration, invasion and epithelial-to-mesenchymal transition (EMT) of breast cancer cells in vitro, whereas forced expression of LINC00467 exhibited the opposite effects. Furthermore, we demonstrated overexpression of LINC00467 promoted tumor growth, while knockdown of LINC00467 inhibited pulmonary metastasis in vivo. Mechanistically, LINC00467 down-regulated miR-138-5p by acting as a miRNA “sponge”. Besides, LINC00467 also up-regulated the protein level of lin-28 homolog B (LIN28B) via a direct interaction. A higher expression level of LINC00467 was observed in breast cancer tissues as compared to the adjacent normal counterparts and elevated LINC00467 predicted poor overall survival. Our findings suggest LINC00467 promotes progression of breast cancer through interacting with miR-138-5p and LIN28B directly. LINC00467 may serve as a potential candidate for the diagnosis and treatment of breast cancer.

scholarly journals E2F1 and epigenetic modifiers orchestrate breast cancer progression by regulating oxygen-dependent ESRP1 expression

Oncogenesis ◽  
2021 ◽  
Vol 10 (8) ◽  
Author(s):  
Cheemala Ashok ◽  
Neha Ahuja ◽  
Subhashis Natua ◽  
Jharna Mishra ◽  
Atul Samaiya ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Rna Binding ◽  
Breast Cancer Progression ◽  
Regulatory Mechanisms ◽  
Binding Motif ◽  
Primary Tumors ◽  
Mesenchymal Transition

AbstractEpithelial splicing regulatory protein 1 (ESRP1) is an RNA binding protein that governs the alternative splicing events related to epithelial phenotypes. ESRP1 contributes significantly at different stages of cancer progression. ESRP1 expression is substantially elevated in carcinoma in situ compared to the normal epithelium, whereas it is drastically ablated in cancer cells within hypoxic niches, which promotes epithelial to mesenchymal transition (EMT). Although a considerable body of research sought to understand the EMT-associated ESRP1 downregulation, the regulatory mechanisms underlying ESRP1 upregulation in primary tumors remained largely uncharted. This study seeks to unveil the regulatory mechanisms that spatiotemporally fine-tune the ESRP1 expression during breast carcinogenesis. Our results reveal that an elevated expression of transcription factor E2F1 and increased CpG hydroxymethylation of the E2F1 binding motif conjointly induce ESRP1 expression in breast carcinoma. However, E2F1 fails to upregulate ESRP1 despite its abundance in oxygen-deprived breast cancer cells. Mechanistically, impelled by the hypoxia-driven reduction of tet methylcytosine dioxygenase 3 (TET3) activity, CpG sites across the E2F1 binding motif lose the hydroxymethylation marks while gaining the de novo methyltransferase-elicited methylation marks. These two oxygen-sensitive epigenetic events work in concert to repel E2F1 from the ESRP1 promoter, thereby diminishing ESRP1 expression under hypoxia. Furthermore, E2F1 skews the cancer spliceome by upregulating splicing factor SRSF7 in hypoxic breast cancer cells. Our findings provide previously unreported mechanistic insights into the plastic nature of ESRP1 expression and insinuate important implications in therapeutics targeting breast cancer progression.

scholarly journals HOXB7 induces oncogenic transformation in NMuMG cells via JAK2-STAT3 signaling

2021 ◽  
Author(s):  
Mai Sakamoto ◽  
Jun Nakayama ◽  
Atsuka Matsui ◽  
Jiro Fujimoto ◽  
Naoki Goshima ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Cancer Drug ◽  
Oncogenic Transformation ◽  
Her2 Positive ◽  
Mesenchymal Transition ◽  
Public Data

The homeobox family genes are often dysregulated in various cancer types. In particular, HOXB7 overexpression contributes to cancer progression by promoting epithelial to mesenchymal transition, anti-cancer drug resistance, and metastasis of breast, hepatocellular and gastric cancer. Although the relationship between HOXB7 and cancer progression has been described, the role of HOXB7 in cancer initiation is unclear. In this study, we showed that HOXB7 overexpression induced oncogenic transformation in vitro and in vivo through the activation of JAK-STAT signaling and enhanced the expression of ERBB2 in NMuMG cells. In public data sets, HER2-positive breast cancer highly expressed HOXB7, the expression of which was correlated with poor prognosis in breast cancer cohorts. Furthermore, the amplification of HOXB7 on 17q23.32 was found to be a potential clinical diagnostic marker.

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