scholarly journals The HIF target MAFF promotes tumor invasion and metastasis through IL11 and STAT3 signaling

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Eui Jung Moon ◽  
Stephano S. Mello ◽  
Caiyun G. Li ◽  
Jen-Tsan Chi ◽  
Kaushik Thakkar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Invasion ◽  
Critical Role ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Invasion And Metastasis ◽  
Stat3 Signaling ◽  
Inducible Genes ◽  
Transcriptional Target

AbstractHypoxia plays a critical role in tumor progression including invasion and metastasis. To determine critical genes regulated by hypoxia that promote invasion and metastasis, we screen fifty hypoxia inducible genes for their effects on invasion. In this study, we identify v-maf musculoaponeurotic fibrosarcoma oncogene homolog F (MAFF) as a potent regulator of tumor invasion without affecting cell viability. MAFF expression is elevated in metastatic breast cancer patients and is specifically correlated with hypoxic tumors. Combined ChIP- and RNA-sequencing identifies IL11 as a direct transcriptional target of the heterodimer between MAFF and BACH1, which leads to activation of STAT3 signaling. Inhibition of IL11 results in similar levels of metastatic suppression as inhibition of MAFF. This study demonstrates the oncogenic role of MAFF as an activator of the IL11/STAT3 pathways in breast cancer.

scholarly journals CXCR2: A Novel Mediator of Mammary Tumor Bone Metastasis

2019 ◽  
Vol 20 (5) ◽  
pp. 1237 ◽  
Author(s):  
Bhawna Sharma ◽  
Kalyan Nannuru ◽  
Sugandha Saxena ◽  
Michelle Varney ◽  
Rakesh Singh
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
Tumor Cell ◽  
Cancer Patients ◽  
Mammary Tumor ◽  
Critical Role ◽  
Breast Cancer Patients ◽  
Mammary Tumor Cell ◽  
Primary Tumors

Most breast cancer patients die due to bone metastasis. Although metastasis accounts for 5% of the breast cancer cases, it is responsible for most of the deaths. Sometimes even before the detection of a primary tumor, most of the patients have bone and lymph node metastasis. Moreover, at the time of death, breast cancer patients have the bulk of the tumor burden in their bones. Therapy options are available for the treatment of primary tumors, but there are minimal options for treating breast cancer patients who have bone metastasis. C-X-C motif chemokine receptor type 2 (CXCR2) receptor-mediated signaling has been shown to play a critical role during bone-related inflammations and its ligands C-X-C motif chemokine ligand 6 (CXCL6) and 8 (CXCL8) aid in the resorption of bone during bone metastasis. In this study, we tested the hypothesis that CXCR2 contributes to mammary tumor-induced osteolysis and bone metastasis. In the present study, we examined the role of both tumor cell-derived and host-derived CXCR2 in influencing mammary tumor cell bone metastasis. For understanding the role of tumor cell-derived CXCR2, we utilized Cl66 CXCR2 knockdown (Cl66-shCXCR2) and Cl66-Control cells (Cl66-Control) and observed a significant decrease in tumor growth and tumor-induced osteolysis in Cl66-shCXCR2 cells in comparison with the Cl66-Control cells. Next, for understanding the role of host-derived CXCR2, we utilized mice with genomic knockdown of CXCR2 (Cxcr2−/−) and injected Cl66-Luciferase (Cl66-Luc) or 4T1-Luciferase (4T1-Luc) cells. We observed decreased bone destruction and metastasis in the bone of Cxcr2−/− mice. Our data suggest the importance of both tumor cell- and host-derived CXCR2 signaling in the bone metastasis of breast cancer cells.

scholarly journals S100A4 released from highly bone-metastatic breast cancer cells plays a critical role in osteolysis

Bone Research ◽  
2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Haemin Kim ◽  
Bongjun Kim ◽  
Sang Il Kim ◽  
Hyung Joon Kim ◽  
Brian Y. Ryu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
Bone Loss ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cancer Metastasis ◽  
Critical Role ◽  
Bone Destruction ◽  
Metastatic Breast ◽  
Breast Cancer Patients

Abstract Bone destruction induced by breast cancer metastasis causes severe complications, including death, in breast cancer patients. Communication between cancer cells and skeletal cells in metastatic bone microenvironments is a principal element that drives tumor progression and osteolysis. Tumor-derived factors play fundamental roles in this form of communication. To identify soluble factors released from cancer cells in bone metastasis, we established a highly bone-metastatic subline of MDA-MB-231 breast cancer cells. This subline (mtMDA) showed a markedly elevated ability to secrete S100A4 protein, which directly stimulated osteoclast formation via surface receptor RAGE. Recombinant S100A4 stimulated osteoclastogenesis in vitro and bone loss in vivo. Conditioned medium from mtMDA cells in which S100A4 was knocked down had a reduced ability to stimulate osteoclasts. Furthermore, the S100A4 knockdown cells elicited less bone destruction in mice than the control knockdown cells. In addition, administration of an anti-S100A4 monoclonal antibody (mAb) that we developed attenuated the stimulation of osteoclastogenesis and bone loss by mtMDA in mice. Taken together, our results suggest that S100A4 released from breast cancer cells is an important player in the osteolysis caused by breast cancer bone metastasis.

Abstract C17: Role of miR-135b in gemcitabine sensitivity for metastatic breast cancer patients

2015 ◽  
Author(s):  
Anna Tessari ◽  
Dario Palmieri ◽  
Giovanni Nigita ◽  
Dario Veneziano ◽  
Sara Cresta ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Metastatic Breast ◽  
Breast Cancer Patients

Role of fulvestrant in the treatment of postmenopausal metastatic breast cancer patients

2016 ◽  
Vol 9 (9) ◽  
pp. 1153-1161 ◽  
Author(s):  
Francesca Poggio ◽  
Matteo Lambertini ◽  
Eva Blondeaux ◽  
Marina Vaglica ◽  
Alessia Levaggi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Metastatic Breast ◽  
Breast Cancer Patients

scholarly journals Role of Curcumin in reducing toxicity and adverse effects in locally advanced and metastatic breast cancer patients

2019 ◽  
Vol 30 ◽  
pp. vi126-vi127
Author(s):  
Shekhar Goyal ◽  
Surender Kr Beniwal ◽  
H.S. Kumar ◽  
Dhruv Kumar ◽  
B.C. Das
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Adverse Effects ◽  
Cancer Patients ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Breast Cancer Patients

scholarly journals Exosomal miR-1246 is Involved in Tumorigenesis by Targeting THRB in Breast Cancer

2021 ◽  
Author(s):  
Jie Zhu ◽  
Xiaoying Chen ◽  
Fengxiang Xi ◽  
Lei Zhao ◽  
Yichao Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Target Genes ◽  
Metastatic Breast ◽  
Functional Enrichment ◽  
Breast Cancer Patients ◽  
Invasion And Migration ◽  
Kaplan Meier ◽  
Exosomal Mirnas ◽  
And Migration

Abstract Background: Exosomal miRNAs have drawn increasing attention as tumor biomarkers involving in tumorigenesis due to their stability. The aim of this study was to analyze the role of exosomal miR-1246 in breast cancer.Methods: The differentially expressed (DE) miRNAs in exosomes from the serum of breast cancer patients and healthy controls were investigated using RNA-seq. The potential pathogenic target genes and functional enrichment of these miRNAs were explored using bioinformatics. Additionally, the role of miR-1246 in migration, invasion and proliferation were investigated in breast cancer cells. The expression of THRB were detected by QRT-PCR. Kaplan-Meier plotter was used to perform survival analysis.Results: The results showed that the level of exosomal miR-1246 was significantly higher in breast cancer than in the control. MiR-1246 mimic treatment promoted invasion and migration in MDA-MB-231 cells by targeting THRB. Kaplan-Meier survival curves showed that patients with high miR-1246 expression exhibited poor OS compared with patients with low miR-1246 expression, especially those with metastatic breast cancer.Conclusion: Our study provides a better understanding of exosomal miR-1246 in the process of breast cancer. Exosomal miR-1246 could be a potential prognostic biomarker for breast carcinoma.

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