HIF1A induces expression of the WASF3 metastasis-associated gene under hypoxic conditions.

International Journal of Cancer. Journal International Du Cancer
Pushpankur GhoshalJohn K Cowell

Abstract

The WASF3 (WAVE3) gene is an important mediator of cell motility, invasion and metastasis and is expressed at high levels in some advanced stage tumors. In our survey of breast cancer cells, we now demonstrate that exposure to hypoxic conditions increases WASF3 expression levels in MDA231, SKBR3 and MCF7 cells. The WASF3 promoter region contains HIF1A response elements (HRE). ChIP assays demonstrate that HIF1A binds to these HRE elements in the promoter region, and luciferase reporter assays using the WASF3 gene minimal promoter shows that hypoxia results in its upregulation. Phosphorylation of WASF3 is required for its ability to affect invasion and increased phosphoactivation of WASF3 is also seen in cells challenged with hypoxia. These cells also show increased motility in the scratch wound assay. Cells in which WASF3 has been knocked down show no response to hypoxia as expected, implicating the specificity of the hypoxic response to WASF3. Overall, these experiments demonstrate WASF3 is a HIF1A-regulated gene and suggests a mechanism to explain the observation of elevated expression of WASF3 in advanced stage tumors.

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Citations

Nov 8, 2013·Breast Cancer Research and Treatment·Molly A TaylorKhalid Sossey-Alaoui
Nov 3, 2012·Seminars in Cell & Developmental Biology·Khalid Sossey-Alaoui
Feb 11, 2015·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yingjie JiWenjin Zhang
Jul 7, 2017·Cancer Growth and Metastasis·John K CowellEileen J Kennedy
May 1, 2019·Future Oncology·Yanli NieXinjun Liang
Jul 20, 2016·Cancer Research·Yong TengJohn K Cowell
Jan 21, 2021·International Journal of Molecular Sciences·Reid Loveless, Yong Teng
Feb 18, 2021·Scientific Reports·Urna KansakarKhalid Sossey-Alaoui
May 4, 2020·The American Journal of the Medical Sciences·Yanli NieFuxiang Zhou

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