Details

Autor(en) / Beteiligte

• Altemus, Megan A
• Goo, Laura E
• Little, Andrew C
• Yates, Joel A
• Cheriyan, Hannah G
• Wu, Zhi Fen
• Merajver, Sofia D
• Rishi, Arun

Titel

Breast cancers utilize hypoxic glycogen stores via PYGB, the brain isoform of glycogen phosphorylase, to promote metastatic phenotypes

Ist Teil von

• PloS one, 2019-09, Vol.14 (9), p.e0220973-e0220973

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.