Oscillatory hypoxia induced gene expression predicts low survival in human breast cancer patients

Yasir Suhail; Yamin Liu; Wenqiang Du; Junaid Afzal; Xihua Qiu; Amina Atiq; Paola Vera‐Licona; Eran Agmon; Kshitiz

doi:10.1002/mc.23810

journal article Aug 16, 2024

Oscillatory hypoxia induced gene expression predicts low survival in human breast cancer patients

Yasir Suhail Yamin Liu

Wenqiang Du Junaid Afzal Xihua Qiu Amina Atiq Paola Vera‐Licona Eran Agmon

Kshitiz

Molecular Carcinogenesis Vol. 63 No. 12 pp. 2305-2315 · Wiley

View at Publisher Save 10.1002/mc.23810

Abstract

AbstractHypoxia is one of the key factors in the tumor microenvironment regulating nearly all steps in the metastatic cascade in many cancers, including in breast cancer. The hypoxic regions can however be dynamic with the availability of oxygen fluctuating or oscillating. The canonical response to hypoxia is relayed by transcription factor Hypoxia‐Inducible Factor 1 (HIF‐1), which is stabilized in hypoxia and acts as the master regulator of a large number of downstream genes. However, HIF‐1 transcriptional activity can also fluctuate either due to unstable hypoxia, or by lactate mediated noncanonical degradation of HIF‐1. Our understanding of how oscillatory hypoxia or HIF‐1 activity specifically influences cancer malignancy is very limited. Here, using MDA‐MB‐231 cells as a model of triple negative breast cancer characterized by severe hypoxia, we measured the gene expression changes induced specifically by oscillatory hypoxia. We found that oscillatory hypoxia can specifically regulate gene expression differently, and at times opposite to stable hypoxia. Using the Cancer Genome Atlas RNAseq data of human cancer samples, we show that the oscillatory specific gene expression signature in MDA‐MB‐231 is enriched in most human cancers, and prognosticates low survival in breast cancer patients. In particular, we found that oscillatory hypoxia, unlike stable hypoxia, induces unfolded protein folding response in cells resulting in gene expression predicting reduced survival.

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Metrics

7

Citations

25

References

Details

Published: Aug 16, 2024
Vol/Issue: 63(12)
Pages: 2305-2315
License: View

Authors

Y

Yasir Suhail

Department of Biomedical Engineering University of Connecticut Health Farmington Connecticut USA; Center for Cell Analysis and Modeling University of Connecticut Health Farmington Connecticut USA; Department of Biomedical Engineering University of Connecticut Storrs Connecticut USA

Y

Yamin Liu

Department of Biomedical Engineering University of Connecticut Health Farmington Connecticut USA; Department of Biomedical Engineering University of Connecticut Storrs Connecticut USA

W

Wenqiang Du

Department of Biomedical Engineering University of Connecticut Health Farmington Connecticut USA

J

Junaid Afzal

Department of Medicine University of California San Francisco San Francisco California USA

X

Xihua Qiu

Department of Biomedical Engineering University of Connecticut Health Farmington Connecticut USA

A

Amina Atiq

Department of Biomedical Engineering University of Connecticut Storrs Connecticut USA

P

Paola Vera‐Licona

Center for Cell Analysis and Modeling University of Connecticut Health Farmington Connecticut USA

E

Eran Agmon

Center for Cell Analysis and Modeling University of Connecticut Health Farmington Connecticut USA

K

Kshitiz

Department of Biomedical Engineering University of Connecticut Health Farmington Connecticut USA; Center for Cell Analysis and Modeling University of Connecticut Health Farmington Connecticut USA; Department of Biomedical Engineering University of Connecticut Storrs Connecticut USA

Funding

National Cancer Institute

Cite This Article

Yasir Suhail, Yamin Liu, Wenqiang Du, et al. (2024). Oscillatory hypoxia induced gene expression predicts low survival in human breast cancer patients. Molecular Carcinogenesis, 63(12), 2305-2315. https://doi.org/10.1002/mc.23810

Oscillatory hypoxia induced gene expression predicts low survival in human breast cancer patients

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