The Tumor Suppressor Runx1 is a Negative Regulator of Hypoxia-Inducible Factor-1α (HIF-1α) in Breast Cancer Cells
Mak, Lena L
Mak, Lena L
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Abstract
The tumor response to oxygen deficiency (hypoxia) is associated with cancer cell survival, metastasis and resistance to chemotherapy. Hypoxia induces the stabilization of Hypoxia-Inducible Factor-1α (HIF-1α) which mediates the expression of genes that promote survival and angiogenesis. Runx1 is a transcription factor that is downregulated in aggressive breast cancer cells. In a preliminary RNA-Seq screen, the depletion of Runx1 resulted in upregulation of hypoxia-regulated genes. To explore this mechanism, we tested the hypothesis that Runx1 is a negative regulator of HIF-1α. To determine if the loss of Runx1 activity leads to an increase in HIF-1α protein level, MCF10A breast cancer cells were exposed to a Runx1 inhibitor, and levels of HIF-1α protein were measured by Western blot. Results showed that Runx1 inhibition significantly increased the level of HIF-1α, even in the absence of a proteasome inhibitor (p<0.05, n=5). In preliminary experiments, inhibition of Runx1 did not affect HIF-1α mRNA level, measured by qPCR. Future experiments will confirm the effects of Runx1 inhibition on HIF-α and will also measure other hypoxia-related genes. Additionally, overexpression of Runx1 is predicted to prevent the hypoxia-induction of HIF-1α. A better understanding of the regulation of hypoxia responses has important implications for developing effective cancer therapies.
Description
3:00pm-5:00pm
Undergraduate
Undergraduate
Date
2020-01-01