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

Abstract P3-03-01: Intracranial PDX models of breast cancer metastasis

2016 ◽  
Author(s):  
CH Nielsen ◽  
MK Nedergaard ◽  
MJ Wick ◽  
K Papadopoulos ◽  
AW Tolcher ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Pdx Models

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 A New Mouse Model for the Study of Human Breast Cancer Metastasis

PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
pp. e47995 ◽  
Author(s):  
Elizabeth Iorns ◽  
Katherine Drews-Elger ◽  
Toby M. Ward ◽  
Sonja Dean ◽  
Jennifer Clarke ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mouse Model ◽  
Human Breast Cancer ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Human Breast

scholarly journals The AIB1 Oncogene Promotes Breast Cancer Metastasis by Activation of PEA3-Mediated Matrix Metalloproteinase 2 (MMP2) and MMP9 Expression

2008 ◽  
Vol 28 (19) ◽  
pp. 5937-5950 ◽  
Author(s):  
Li Qin ◽  
Lan Liao ◽  
Aisling Redmond ◽  
Leonie Young ◽  
Yuhui Yuan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Matrix Metalloproteinase ◽  
Tumor Cells ◽  
Lung Metastasis ◽  
Cancer Metastasis ◽  
Three Dimensional ◽  
Mammary Tumorigenesis ◽  
Breast Cancer Metastasis ◽  
Matrix Metalloproteinase 2 ◽  
Human Breast

ABSTRACT Amplified-in-breast cancer 1 (AIB1) is an overexpressed transcriptional coactivator in breast cancer. Although overproduced AIB1 is oncogenic, its role and underlying mechanisms in metastasis remain unclear. Here, mammary tumorigenesis and lung metastasis were investigated in wild-type (WT) and AIB1−/− mice harboring the mouse mammary tumor virus-polyomavirus middle T (PyMT) transgene. All WT/PyMT mice developed massive lung metastasis, but AIB1−/−/PyMT mice with comparable mammary tumors had significantly less lung metastasis. The recipient mice with transplanted AIB1−/−/PyMT tumors also had much less lung metastasis than the recipient mice with transplanted WT/PyMT tumors. WT/PyMT tumor cells expressed mesenchymal markers such as vimentin and N-cadherin, migrated and invaded rapidly, and formed disorganized cellular masses in three-dimensional cultures. In contrast, AIB1−/−/PyMT tumor cells maintained epithelial markers such as E-cadherin and ZO-1, migrated and invaded slowly, and still formed polarized acinar structures in three-dimensional cultures. Molecular analyses revealed that AIB1 served as a PEA3 coactivator and formed complexes with PEA3 on matrix metalloproteinase 2 (MMP2) and MMP9 promoters to enhance their expression in both mouse and human breast cancer cells. In 560 human breast tumors, AIB1 expression was found to be positively associated with PEA3, MMP2, and MMP9. These findings suggest a new alternative strategy for controlling the deleterious roles of these MMPs in breast cancer by inhibiting their upstream coregulator AIB1.

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