Collagen Prolyl Hydroxylases are Essential for Breast Cancer Metastasis
Daniele M. Gilkes,Pallavi Chaturvedi,Saumendra Bajpai,Carmen Chak-Lui Wong,Hong Wei,Stephen Pitcairn,Maimon E. Hubbi,Denis Wirtz,Gregg L. Semenza +8 more
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TLDR
It is demonstrated that hypoxia-inducible factor 1 activates the transcription of genes encoding collagen prolyl hydroxylases that are critical for collagen deposition by breast cancer cells, resulting in enhanced invasion and metastasis to lymph nodes and lungs.Abstract:
The presence of hypoxia and fibrosis within the primary tumor are two major risk factors for metastasis of human breast cancer. In this study, we demonstrate that hypoxia-inducible factor 1 activates the transcription of genes encoding collagen prolyl hydroxylases that are critical for collagen deposition by breast cancer cells. We show that expression of collagen prolyl hydroxylases promotes cancer cell alignment along collagen fibers, resulting in enhanced invasion and metastasis to lymph nodes and lungs. Finally, we establish the prognostic significance of collagen prolyl hydroxylase mRNA expression in human breast cancer biopsies and show that ethyl 3,4-dihydroxybenzoate, a prolyl hydroxylase inhibitor, decreases tumor fibrosis and metastasis in a mouse model of breast cancer.read more
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PML promotes metastasis of triple-negative breast cancer through transcriptional regulation of HIF1A target genes
Manfredi Ponente,Letizia Campanini,Roberto Cuttano,Andrea Piunti,Giacomo A. Delledonne,Nadia Coltella,Roberta Valsecchi,Alessandra Villa,Ugo Cavallaro,Linda Pattini,Claudio Doglioni,Rosa Bernardi +11 more
TL;DR: It is found that the promyelocytic leukemia protein PML exerts a prometastatic function in TNBC that can be targeted by arsenic trioxide, and pharmacological inhibition of PML with arsenic Trioxide delays tumor growth, impairs TNBC metastasis, and cooperates with chemotherapy by preventing metastatic dissemination.
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The Metabolic Mechanisms of Breast Cancer Metastasis.
TL;DR: The role of metabolism in the progression and metastasis of breast cancer is gradually being emphasized as mentioned in this paper, however, the regulatory mechanisms that conduce to cancer metastasis by metabolic reprogramming in breast cancer have not been expounded.
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Comparative analysis of transcriptomics based hypoxia signatures in head- and neck squamous cell carcinoma.
Bouchra Tawk,Christian Schwager,Oliver Deffaa,Gerhard Dyckhoff,Rolf Warta,Annett Linge,Mechthild Krause,Wilko Weichert,Michael Baumann,Christel Herold-Mende,Jürgen Debus,Amir Abdollahi +11 more
TL;DR: This is the first independent proof for the feasibility of hypoxia gene expression signatures as a prognostic tool in HNSCC patients.
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Hypoxia-inducible factors: cancer progression and clinical translation
TL;DR: In this paper , the mechanisms and consequences of HIF activation in cancer cells are presented and the current status and future prospects of small-molecule HIF inhibitors for use as cancer therapeutics are discussed.
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LOXL4 knockdown enhances tumor growth and lung metastasis through collagen-dependent extracellular matrix changes in triple-negative breast cancer
TL;DR: It is demonstrated that weak LOXL4 expression leads to remodeling of the extracellular matrix through induction of collagen synthesis, deposition, and structural changes and is associated with poor clinical outcomes in triple-negative breast cancer.
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TL;DR: The ability to integrate information across platforms provided key insights into previously defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity.
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Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension
TL;DR: Hypoxia-inducible factor 1 (HIF-1) is found in mammalian cells cultured under reduced O2 tension and is necessary for transcriptional activation mediated by the erythropoietin gene enhancer in hypoxic cells.
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