PRRX2 as a novel TGF-β-induced factor enhances invasion and migration in mammary epithelial cell and correlates with poor prognosis in breast cancer

Molecular Carcinogenesis
Yu-Lin JuangHuang-Chun Lien

Abstract

TGF-β and cancer progression share a multifaceted relationship. Despite the knowledge of TGF-β biology in the development of cancer, several factors that mediate the cancer-promoting role of TGF-β continue to be identified. This study aimed to identify and characterise novel factors potentially related to TGF-β-mediated tumour aggression in breast cells. We treated the human mammary epithelial cell line MCF10A with TGF-β and identified TGF-β-dependent upregulation of PRRX2, the gene encoding paired-related homeobox 2 transcription factor. Overexpression of PRRX2 enhanced migration, invasion and anchorage-independent growth of MCF10A cells and induced partial epithelial mesenchymal transition (EMT), as determined by partial fibroblastoid morphology of cells, upregulation of EMT markers and partially disrupted acinar structure in a three-dimensional culture. We further identified PLAT, the gene encoding tissue-type plasminogen activator (tPA), as the highest differentially expressed gene in PRRX2-overexpressing MCF10A cells, and demonstrated direct binding and transactivation of the PLAT promoter by PRRX2. Furthermore, PLAT knockdown inhibited PRRX2-mediated enhanced migration and invasion, suggesting that tPA may mediate PRRX2-i...Continue Reading

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Citations

Jul 2, 2016·Journal of Clinical Medicine·Aristidis Moustakas, Carl-Henrik Heldin
Jul 10, 2019·Molecular & Cellular Proteomics : MCP·Weiping MaPei Wang
Feb 21, 2019·Investigative Ophthalmology & Visual Science·Justin Ma, Peter Lwigale
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Jan 15, 2021·World Journal of Surgical Oncology·Zhengyu FangWenxi Yan
Aug 9, 2019·Molecular & Cellular Proteomics : MCP·Weiping MaPei Wang

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