scholarly journals Tumor suppressor HIC1 is synergistically compromised by cancer-associated fibroblasts and tumor cells through the IL-6/pSTAT3 axis in breast cancer

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Xueqing Sun ◽  
Qing Qu ◽  
Yimin Lao ◽  
Mi Zhang ◽  
Xiaoling Yin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Cell Line ◽  
Cancer Tissue ◽  
Cancer Associated Fibroblasts ◽  
Autocrine Signaling ◽  
Stromal Fibroblasts ◽  
Signal Transducers

Abstracts Background Interleukin-6 (IL-6) is commonly highly secreted in the breast cancer (BrCA) microenvironment and implicated in disease development. In this study, we aimed to determine the role of the IL-6/pSTAT3/HIC1 axis in the breast cancer microenvironment, including in cancer-associated fibroblasts (CAFs) and breast cancer cells. Methods Stromal fibroblasts from the breast cancer tissue were isolated, and the supernatants of the fibroblasts were analyzed. Recombinant human IL-6 (rhIL-6) was applied to simulate the effect of CAF-derived IL-6 to study the mechanism of HIC1 (tumor suppressor hypermethylated in cancer 1) downregulation. IL-6 was knocked down in the high IL-6-expressing BrCA cell line MDA-MB-231, which enabled the investigation of the IL-6/pSTAT3/HIC1 axis in the autocrine pathway. Results Increased IL-6 was found in the supernatant of isolated CAFs, which suppressed HIC1 expression in cancer cells and promoted BrCA cell proliferation. After stimulating the BrCA cell line SK-BR-3 (where IL-6R is highly expressed) with rhIL-6, signal transducers and activators of transcription 3 (STAT3) was found to be phosphorylated and HIC1 decreased, and a STAT3 inhibitor completely rescued HIC1 expression. Moreover, HIC1 was restored upon knocking down IL-6 expression in MDA-MB-231 cells, accompanied by a decrease in STAT3 activity. Conclusions These findings indicate that IL-6 downregulates the tumor suppressor HIC1 and promotes BrCA development in the tumor microenvironment through paracrine or autocrine signaling.

scholarly journals Signalling mechanisms regulating phenotypic changes in breast cancer cells

2015 ◽  
Vol 35 (2) ◽  
Author(s):  
Natalia Volinsky ◽  
Cormac J. McCarthy ◽  
Alex von Kriegsheim ◽  
Nina Saban ◽  
Mariko Okada-Hatakeyama ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Breast Cancer Cells ◽  
Breast Cancer Tissue ◽  
Cancer Tissue ◽  
Phenotypic Changes ◽  
Model Cell ◽  
Accumulation Of Lipids

Excessive production and accumulation of lipids is often observed in breast cancer tissue. In the current study, we investigate signalling mechanisms regulating this process using a model cell line.

scholarly journals Differential tumor biological role of the tumor suppressor KAI1 and its splice variant in human breast cancer cells

Oncotarget ◽  
2018 ◽  
Vol 9 (5) ◽  
pp. 6369-6390 ◽  
Author(s):  
Julia Miller ◽  
Tobias F. Dreyer ◽  
Anne Sophie Bächer ◽  
Eva-Kathrin Sinner ◽  
Christine Heinrich ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Splice Variant ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Biological Role ◽  
Human Breast Cancer Cells ◽  
Human Breast

scholarly journals Human drug efflux transporter ABCC5 confers acquired resistance to pemetrexed in breast cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jihui Chen ◽  
Zhipeng Wang ◽  
Shouhong Gao ◽  
Kejin Wu ◽  
Fang Bai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Abc Transporters ◽  
Breast Cancer Cells ◽  
Breast Cancer Treatment ◽  
Control Group ◽  
Mcf 7

Abstract Aim Pemetrexed, a new generation antifolate drug, has been approved for the treatment of locally advanced or metastatic breast cancer. However, factors affecting its efficacy and resistance have not been fully elucidated yet. ATP-binding cassette (ABC) transporters are predictors of prognosis as well as of adverse effects of several xenobiotics. This study was designed to explore whether ABC transporters affect pemetrexed resistance and can contribute to the optimization of breast cancer treatment regimen. Methods First, we measured the expression levels of ABC transporter family members in cell lines. Subsequently, we assessed the potential role of ABC transporters in conferring resistance to pemetrexed in primary breast cancer cells isolated from 34 breast cancer patients and the role of ABCC5 in mediating pemetrexed transport and apoptotic pathways in MCF-7 cells. Finally, the influence of ABCC5 expression on the therapeutic effect of pemetrexed was evaluated in an in vivo xenograft mouse model of breast cancer. Results The expression levels of ABCC2, ABCC4, ABCC5, and ABCG2 significantly increased in the pan-resistant cell line, and the ABCC5 level in the MCF-7-ADR cell line was 5.21 times higher than that in the control group. ABCC5 expression was inversely correlated with pemetrexed sensitivity (IC50, r = 0.741; p < 0.001) in breast cancer cells derived from 34 patients. Furthermore, we found that the expression level of ABCC5 influenced the efflux and cytotoxicity of pemetrexed in MCF-7 cells, with IC50 values of 0.06 and 0.20 μg/mL in ABCC5 knockout and over-expression cells, respectively. In the in vivo study, we observed that ABCC5 affected the sensitivity of pemetrexed in breast tumor-bearing mice, and the tumor volume was much larger in the ABCC5-overexpressing group than in the control group when compared with their own initial volumes (2.7-fold vs. 1.3-fold). Conclusions Our results indicated that ABCC5 expression was associated with pemetrexed resistance in vitro and in vivo, and it may serve as a target or biomarker for the optimization of pemetrexed regimen in breast cancer treatment.

scholarly journals MicroRNA-200c Overexpression in Cancer-Associated Fibroblasts Reduces the Invasive Properties of Breast Cancer Cells: An Approach to Molecular Therapy

2021 ◽  
Author(s):  
Nasim Shenavar ◽  
Laleh Shariati ◽  
Mohammad Reza Hakimian ◽  
Shaghayegh Haghjooy Javanmard
Keyword(s):  
Breast Cancer ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Critical Role ◽  
Molecular Therapy ◽  
Cancer Development ◽  
Cancer Associated Fibroblasts ◽  
Cancer Breast ◽  
Aggressive Subtype ◽  
Common Malignancy

Abstract BackgroundThe most common malignancy is breast cancer, among women in the world. Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Cancer associated fibroblasts (CAFs) play a critical role to support tumor cells in all aspect of cancer development such as cell proliferation, migration and angiogenesis. MiRNAs are one of the regulatory molecules that regulate the genes contributing to cell growth, differentiation, migration and apoptosis. Based on other studies, miR-200c, as a tumor suppressor, has low expression levels in cancer associated fibroblasts. In this investigation, effect of miR-200c overexpression was evaluated on proliferation, migration and angiogenesis of TNBC cells. MethodsThe fibroblasts were isolated from normal and cancer breast tissue. MiR-200c expression was assessed using RT PCR in cancer associated fibroblasts (CAFs) and normal fibrobalasts (NFs) and then, were transfected using miR-200c. Finally, its effect on proliferation, migration and angiogenesis of TNBC cells were evaluated. ResultsOur results confirm that in presence of miR-200c transfected fibroblasts, the proliferation, migration and angiogenesis of cancer cells significantly decreased. This effect may be due to the reduction of growth factors provided by CAFs after miRNAs dysregulation. ConclusionThese results suggest miR-200c act as an effective tumor suppressor in many aspects of TNBC cancer development and can be regarded as a potential therapeutic tool for breast cancer in the future.

A novel role of tumor suppressor ZMYND8 in inducing differentiation of breast cancer cells through its dual-histone binding function

2020 ◽  
Vol 45 (1) ◽  
Author(s):  
Shravanti Mukherjee ◽  
Sabyasachi Sen ◽  
Santanu Adhikary ◽  
Amrita Sengupta ◽  
Pratiti Mandal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Histone Binding ◽  
Binding Function

scholarly journals The downregulation of WWOX induces epithelial–mesenchymal transition and enhances stemness and chemoresistance in breast cancer

2018 ◽  
Vol 243 (13) ◽  
pp. 1066-1073 ◽  
Author(s):  
Juan Li ◽  
Jie Liu ◽  
Pingping Li ◽  
Can Zhou ◽  
Peijun Liu
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Tumor Suppressor ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Cell Phenotype ◽  
Ww Domain ◽  
Mesenchymal Transition

WW domain-containing oxidoreductase (WWOX), an important tumor suppressor, is essential for regulating cell proliferation and apoptosis. Our study demonstrates that low level of WWOX is associated with the triple-negative subtype of breast cancer (TNBC), which has higher stem cell phenotype and chemoresistance. We evaluated the role of WWOX in regulation of breast cancer stem cells (BCSC) phenotype and chemoresistance. Our results showed that knockdown of WWOX increases the stemness of breast cancer cells. Meanwhile, downregulation of WWOX induces the epithelial–mesenchymal transition (EMT) and chemoresistance of breast cancer cell lines. Our findings revealed the role of the WWOX in the regulation of the BCSC population and chemotherapeutic sensitivity and may provide insights for the development of more effective therapies targeting cancer stem cells in breast cancer. Impact statement Overcoming resistance to chemotherapy is one of the fundamental issues of clinical treatment and CSCs are responsible for the poor therapeutic effects of chemotherapy. WW domain-containing oxidoreductase (WWOX), an important tumor suppressor, regulates cancer cells’ response to chemotherapy. The major finding of our study is the novel role of WWOX in the chemoresistance of breast cancer through the regulation of cell stemness and EMT. The plasticity may play a crucial role in tumor metastasis, treatment resistance and tumor recurrence. Our findings may shed new light on the alterations of BCSCs and pave the way for the discovery of novel and more effective therapies to treat breast cancer by targeting WWOX.

scholarly journals Apoptotic effect of Physalis minima Linn ethanol extract on breast cancer cells via p53 wild-type and Apaf-1 protein

2020 ◽  
Vol 19 (10) ◽  
pp. 2085-2089
Author(s):  
Handayani Handayani ◽  
Retno Handajani ◽  
Imam Susilo ◽  
Achmad Basori ◽  
Hotimah Masdan Salim
Keyword(s):  
Breast Cancer ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Cell Line ◽  
Breast Cancer Cells ◽  
Ethanol Extract ◽  
Tumor Suppressor Protein ◽  
Tumor Suppressor Protein P53 ◽  
Protein P53 ◽  
Mcf 7

Purpose: To produce an anti-cancer agent from Physalis minima ethanol extract as well as prevent the growth of NMU-induced breast cancer and MCF-7 cell line.Methods: This research used an animal model (Wistar-Furth rats), and cell line used in this study was normal breast-cell line MCF-7. The rats were administered with the ethanol extract of Physalis minima Linn (100, 250 and 400 mg/kg/day) by gavage, once a day for 4 weeks. Meanwhile, MCF-7 cell lines were cultured in medium and incubated in 100 μg/mL of ethanol extract of Physalis minima for 48 h. The samples were analyzed using histology and immunohistochemistry techniques for expression of p53 antibody DO-1 and APAF-1.Results: The results of immunohistological analysis in the breast organ showed that Physalis minima Linn extract significantly (p < 0.05) increased the tumor suppressor protein p53 at doses of 100, 250 and 400 mg/kg/day. In addition, the extract also significantly (p < 0.05) increased APAF-1, which is a gene determining cell death, at doses of 100, 200 and 400 mg/day.Conclusion: Ethanol extract of Physalis minima Linn inhibits the cytotoxic activity of NMU-induced breast cancer by increasing the tumor suppressor protein p53 and APAF-1. Thus, Physalis minima Linn extract can potentially be used as a complementary treatment for inhibiting the growth of breast cancer cells in patients. Keywords: Apoptosis protease-activating factor-1, Breast cancer, MCF-7 cell line, Physalis minima, p53

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