Breast cancers utilize hypoxic glycogen stores via PYGB, the brain isoform of glycogen phosphorylase, to promote metastatic phenotypes
| Autor: | Sofia D. Merajver, Joel A. Yates, Megan Altemus, Zhi Fen Wu, Laura E. Goo, Hannah Cheriyan, Andrew C. Little |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Glycogens Glycobiology Gene Expression Biochemistry Metastasis chemistry.chemical_compound 0302 clinical medicine Breast Tumors Basic Cancer Research Medicine and Health Sciences Protein Isoforms Electron Microscopy Phosphorylase b Neoplasm Metastasis RNA Small Interfering Hypoxia Enzyme Chemistry skin and connective tissue diseases Microscopy Gene knockdown Multidisciplinary Glycogen Chemistry Enzymes 3. Good health Phenotype Oncology Gene Knockdown Techniques 030220 oncology & carcinogenesis Medicine Female RNA Interference medicine.symptom Metabolic Networks and Pathways Research Article Phosphorylases Science Breast Neoplasms Research and Analysis Methods Enzyme Regulation 03 medical and health sciences Glycogen phosphorylase Breast cancer Allosteric Regulation Transferases Cell Line Tumor Breast Cancer Genetics medicine Humans Neoplasm Staging Tumor hypoxia Biology and Life Sciences Cancers and Neoplasms Proteins Cell Biology Hypoxia (medical) medicine.disease 030104 developmental biology Bright Field Imaging Cancer cell Enzymology Cancer research Transmission Electron Microscopy |
| Zdroj: | PLoS ONE, Vol 14, Iss 9, p e0220973 (2019) PLoS ONE |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0220973 |
| Popis: | In breast cancer, tumor hypoxia has been linked to poor prognosis and increased metastasis. Hypoxia activates transcriptional programs in cancer cells that lead to increased motility and invasion, as well as various metabolic changes. One of these metabolic changes, an increase in glycogen metabolism, has been further associated with protection from reactive oxygen species damage that may lead to premature senescence. Here we report that breast cancer cells significantly increase glycogen stores in response to hypoxia. We found that knockdown of the brain isoform of an enzyme that catalyzes glycogen breakdown, glycogen phosphorylase B (PYGB), but not the liver isoform, PYGL, inhibited glycogen utilization in estrogen receptor negative and positive breast cancer cells; whereas both independently inhibited glycogen utilization in the normal-like breast epithelial cell line MCF-10A. Functionally, PYGB knockdown and the resulting inhibition of glycogen utilization resulted in significantly decreased wound-healing capability in MCF-7 cells and a decrease in invasive potential of MDA-MB-231 cells. Thus, we identify PYGB as a novel metabolic target with potential applications in the management and/or prevention of metastasis in breast cancer. |
| Databáze: | OpenAIRE |
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