scholarly journals Transcription factor ATF3 links host adaptive response to breast cancer metastasis

2013 ◽  
Vol 123 (7) ◽  
pp. 2893-2906 ◽  
Author(s):  
Chris C. Wolford ◽  
Stephen J. McConoughey ◽  
Swati P. Jalgaonkar ◽  
Marino Leon ◽  
Anand S. Merchant ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcription Factor ◽  
Adaptive Response ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis

scholarly journals EMT cells increase breast cancer metastasis via paracrine GLI activation in neighbouring tumour cells

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Deepika Neelakantan ◽  
Hengbo Zhou ◽  
Michael U. J. Oliphant ◽  
Xiaomei Zhang ◽  
Lukas M. Simon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Tumour Cells ◽  
Human Breast ◽  
Breast Tumours ◽  
Cancer Models ◽  
Pdx Models

Abstract Recent fate-mapping studies concluded that EMT is not required for metastasis of carcinomas. Here we challenge this conclusion by showing that these studies failed to account for possible crosstalk between EMT and non-EMT cells that promotes dissemination of non-EMT cells. In breast cancer models, EMT cells induce increased metastasis of weakly metastatic, non-EMT tumour cells in a paracrine manner, in part by non-cell autonomous activation of the GLI transcription factor. Treatment with GANT61, a GLI1/2 inhibitor, but not with IPI 926, a Smoothened inhibitor, blocks this effect and inhibits growth in PDX models. In human breast tumours, the EMT-transcription factors strongly correlate with activated Hedgehog/GLI signalling but not with the Hh ligands. Our findings indicate that EMT contributes to metastasis via non-cell autonomous effects that activate the Hh pathway. Although all Hh inhibitors may act against tumours with canonical Hh/GLI signalling, only GLI inhibitors would act against non-canonical EMT-induced GLI activation.

POU1F1 transcription factor promotes breast cancer metastasis via recruitment and polarization of macrophages

2019 ◽  
Vol 249 (3) ◽  
pp. 381-394 ◽  
Author(s):  
Samuel Seoane ◽  
Anxo Martinez‐Ordoñez ◽  
Noemi Eiro ◽  
Pablo Cabezas‐Sainz ◽  
Lucia Garcia‐Caballero ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcription Factor ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis

scholarly journals MSC-Regulated MicroRNAs Converge on the Transcription Factor FOXP2 and Promote Breast Cancer Metastasis

2014 ◽  
Vol 15 (6) ◽  
pp. 762-774 ◽  
Author(s):  
Benjamin G. Cuiffo ◽  
Antoine Campagne ◽  
George W. Bell ◽  
Antonio Lembo ◽  
Francesca Orso ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcription Factor ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Promote Breast Cancer

scholarly journals FOXO3a-driven miRNA signatures suppresses VEGF-A/NRP1 signaling and breast cancer metastasis

Oncogene ◽  
2020 ◽  
Author(s):  
Ying Song ◽  
Shanshan Zeng ◽  
Guopei Zheng ◽  
Danyang Chen ◽  
Pan Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcription Factor ◽  
Cancer Metastasis ◽  
Critical Role ◽  
Ectopic Expression ◽  
Breast Cancer Metastasis ◽  
Metastasis Suppressor ◽  
Breast Cancer Patients ◽  
Signaling Axis

AbstractMetastasis remains the major obstacle to improved survival for breast cancer patients. Downregulation of FOXO3a transcription factor in breast cancer is causally associated with the development of metastasis through poorly understood mechanisms. Here, we report that FOXO3a is functionally related to the inhibition of VEGF-A/NRP1 signaling and to the consequent suppression of breast cancer metastasis. We show that FOXO3a directly induces miR-29b-2 and miR-338 expression. Ectopic expression of miR-29b-2/miR-338 significantly suppresses EMT, migration/invasion, and in vivo metastasis of breast cancer. Moreover, we demonstrate that miR-29b-2 directly targets VEGF-A while miR-338 directly targets NRP1, and show that regulation of miR-29b-2 and miR-338 mediates the ability of FOXO3a to suppress VEGF-A/NRP1 signaling and breast cancer metastasis. Clinically, our results show that the FOXO3a-miR-29b-2/miR-338-VEGF-A/NRP1 axis is dysregulated and plays a critical role in disease progression in breast cancer. Collectively, our findings propose that FOXO3a functions as a metastasis suppressor, and define a novel signaling axis of FOXO3a-miRNA-VEGF-A/NRP1 in breast cancer, which might be potential therapeutic targets for breast cancer.

scholarly journals Involvement of a Transcription factor, Nfe2, in Breast Cancer Metastasis to Bone

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3003
Author(s):  
Di Zhang ◽  
Sadahiro Iwabuchi ◽  
Tomohisa Baba ◽  
Shin-ichi Hashimoto ◽  
Naofumi Mukaida ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcription Factor ◽  
Bone Metastasis ◽  
Cancer Metastasis ◽  
High Growth ◽  
Breast Cancer Metastasis ◽  
Tumor Formation ◽  
Bone Microenvironment ◽  
Tnbc Cell

Patients with triple negative breast cancer (TNBC) is frequently complicated by bone metastasis, which deteriorates the life expectancy of this patient cohort. In order to develop a novel type of therapy for bone metastasis, we established 4T1.3 clone with a high capacity to metastasize to bone after orthotopic injection, from a murine TNBC cell line, 4T1.0. To elucidate the molecular mechanism underlying a high growth ability of 4T1.3 in a bone cavity, we searched for a novel candidate molecule with a focus on a transcription factor whose expression was selectively enhanced in a bone cavity. Comprehensive gene expression analysis detected enhanced Nfe2 mRNA expression in 4T1.3 grown in a bone cavity, compared with in vitro culture conditions. Moreover, Nfe2 gene transduction into 4T1.0 cells enhanced their capability to form intraosseous tumors. Moreover, Nfe2 shRNA treatment reduced tumor formation arising from intraosseous injection of 4T1.3 clone as well as another mouse TNBC-derived TS/A.3 clone with an augmented intraosseous tumor formation ability. Furthermore, NFE2 expression was associated with in vitro growth advantages of these TNBC cell lines under hypoxic condition, which mimics the bone microenvironment, as well as Wnt pathway activation. These observations suggest that NFE2 can potentially contribute to breast cancer cell survival in the bone microenvironment.

Regulation of Runx2 and its signaling pathways by microRNAs in breast cancer metastasis

2020 ◽  
Vol 21 ◽  
Author(s):  
Shivashankar Pranavkrishna ◽  
Ganesh Sanjeev ◽  
Ravishkumar L. Akshaya ◽  
Muthukumar Rohini ◽  
Nagarajan Selvamurugan
Keyword(s):  
Breast Cancer ◽  
Transcription Factor ◽  
Signaling Pathways ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Primary Research ◽  
Research Focus ◽  
Runx2 Expression ◽  
Major Threat

: Posing as a major threat among women globally, breast cancer (BC) emerges as a primary research focus for several researchers. Although various therapeutic regimens are available, there is an increased chance of metastasis of BC cells, which raises the severity of this malignancy. Of multiple preferred secondary targets, metastasis to bone is extensively studied. Besides deemed as a bone transcription factor, Runx2 also acts as a metastatic factor that promotes growth and metastasis of BC cells. Studies have reported the significant role of microRNAs (miRNAs) in BC pathogenesis and metastasis by governing Runx2 expression. Additionally, dysregulation of the signaling pathways, including Wnt/β-catenin, TGF-β, Notch, and PI3K/AKT, have been observed to influence the expression of Runx2 in BC cells. In this review, we have aimed to highlight the regulatory role of miRNAs in targeting Runx2 both directly and indirectly by governing respective signaling pathways during bone metastasis of BC.

scholarly journals Chemotherapy-Exacerbated Breast Cancer Metastasis: A Paradox Explainable by Dysregulated Adaptive-Response

2018 ◽  
Vol 19 (11) ◽  
pp. 3333 ◽  
Author(s):  
Justin Middleton ◽  
Daniel Stover ◽  
Tsonwin Hai
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Adaptive Response ◽  
Cancer Biology ◽  
Cancer Metastasis ◽  
Blood Stream ◽  
Breast Cancer Metastasis ◽  
Host Cells ◽  
Primary Tumors

An emerging picture in cancer biology is that, paradoxically, chemotherapy can actively induce changes that favor cancer progression. These pro-cancer changes can be either inside (intrinsic) or outside (extrinsic) the cancer cells. In this review, we will discuss the extrinsic pro-cancer effect of chemotherapy; that is, the effect of chemotherapy on the non-cancer host cells to promote cancer progression. We will focus on metastasis, and will first discuss recent data from mouse models of breast cancer. Despite reducing the size of primary tumors, chemotherapy changes the tumor microenvironment, resulting in an increased escape of cancer cells into the blood stream. Furthermore, chemotherapry changes the tissue microenvironment at the distant sites, making it more hospitable to cancer cells upon their arrival. We will then discuss the idea and evidence that these devastating pro-metastatic effects of chemotherapy can be explained in the context of adaptive-response. At the end, we will discuss the potential relevance of these mouse data to human breast cancer and their implication on chemotherapy in the clinic.

scholarly journals Transcription Factor C-Jun Modulates GLUT1 in Glycolysis and Breast Cancer Metastasis

2021 ◽  
Author(s):  
Ping Zhu ◽  
Jingjing Lu ◽  
Yue Zhou ◽  
Yabiao Gao ◽  
Shuyi Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Transcription Factor ◽  
Survival Data ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Normal Tissues ◽  
Interactive Analysis ◽  
Kaplan Meier ◽  
Factor C

Abstract As one of the main isoforms of membranous glucose transporters (GLUT), GLUT1 involves tumorigenesis, metastasis and prognosis in a variety of cancers. However, its role in breast cancer metastasis remains to be elucidated. Here we examined its transcriptional and survival data in patients with breast cancer from several independent databases including the Oncomine, Gene Expression Profiling Interactive Analysis, Gene Expression across Normal and Tumor tissue, UALCAN, cBioPortal, Kaplan-Meier Plotter and PROGgeneV2. We found that its mRNA expression was significantly high in cancer tissues, which was associated with metastasis and poor survival. Transcription factor c-Jun might bind to GLUT1 promoter to downregulate its gene expression or mRNA stability, therefore to suppress glycolysis and metastasis. By qRT-PCR, we verified that GLUT1 was significantly increased in 38 paired human breast cancer samples while JUN was decreased. Furthermore, the protein level of GLUT1 was higher in tumor compared to normal tissues through IHC assay. We also performed GO and KEGG analysis of genes related to GLUT1 and JUN to explore underlying pathways. Our results further support that transcription factor c-Jun regulates GLUT1 to influence glycolysis and breast cancer metastasis.

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