Hypoxia Selectively Enhances Integrin α
| Autor: | Julia A, Ju, Inês, Godet, I Chae, Ye, Jungmin, Byun, Hasini, Jayatilaka, Sun Joo, Lee, Lisha, Xiang, Debangshu, Samanta, Meng Horng, Lee, Pei-Hsun, Wu, Denis, Wirtz, Gregg L, Semenza, Daniele M, Gilkes |
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| Rok vydání: | 2016 |
| Předmět: |
Mice
Inbred BALB C Integrin beta1 Breast Neoplasms Hypoxia-Inducible Factor 1 alpha Subunit Xenograft Model Antitumor Assays Cell Hypoxia Article Gene Expression Regulation Neoplastic Cell Movement Mice Inbred NOD Cell Line Tumor Spheroids Cellular Basic Helix-Loop-Helix Transcription Factors Animals Humans Female skin and connective tissue diseases Promoter Regions Genetic Integrin alpha5beta1 |
| Zdroj: | Molecular cancer research : MCR. 15(6) |
| ISSN: | 1557-3125 |
| Popis: | Metastasis is the leading cause of breast cancer (BCa) mortality. Previous studies have implicated hypoxia-induced changes in the composition and stiffness of the extracellular matrix (ECM) in the metastatic process. Therefore, the contribution of potential ECM binding receptors in this process was explored. Using a bioinformatics approach the expression of all integrin receptor subunits, in two independent BCa patient data sets, were analyzed to determine if integrin status correlates with a validated hypoxiainducible gene signature. Subsequently, a large panel of breast cancer cell lines were used to validate that hypoxia induces the expression of integrin's that bind to collagen (ITGA1, ITGA11, ITGB1) and fibronectin (ITGA5, ITGB1). Hypoxia-inducible factors (HIF-1 and HIF-2) are directly required for ITGA5 induction under hypoxic conditions, which leads to enhanced migration and invasion of single cells within a multicellular 3D tumor spheroid but did not affect migration in a 2D microenvironment. ITGB1 expression requires HIF-1α, but not HIF-2α, for hypoxic induction in breast cancer cells. ITGA5 (α5 subunit) is required for metastasis to lymph nodes and lungs in breast cancer models and high ITGA5 expression in clinical biopsies is associated with an increased risk of mortality. |
| Databáze: | OpenAIRE |
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