HIF1α-Induced by Lysophosphatidic Acid Is Stabilized via Interaction with MIF and CSN5

PloS One
Yi Ran NoC Chris Yun

Abstract

Macrophage migration inhibitory factor (MIF) is a cytokine that has broad effects on immune system and inflammatory response. A growing body of evidence implicates the role of MIF in tumor growth and metastasis. Lysophosphatidic acid (LPA), a bioactive lipid mediator, regulates colon cancer cell proliferation, invasion, and survival through LPA2 receptor. Loss of LPA2 results in decreased expression of MIF in a rodent model of colon cancer, but the mechanism of MIF regulation by LPA is yet to be determined. In this study, we show that LPA transcriptionally regulates MIF expression in colon cancer cells. MIF knockdown decreased LPA-mediated proliferation of HCT116 human adenocarcinoma cells without altering the basal proliferation rates. Conversely, extracellular recombinant MIF stimulated cell proliferation, suggesting that the effect of MIF may in part be mediated through activation of surface receptor. We have shown recently that LPA increases hypoxia-inducible factor 1α (HIF1α) expression. We found that MIF regulation by LPA was ablated by knockdown of HIF1α, indicating that MIF is a transcriptional target of HIF1α. Conversely, knockdown of MIF ablated an increase in HIF1α expression in LPA-treated cells, suggesting a recipr...Continue Reading

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Citations

Jan 19, 2016·Medicinal Research Reviews·Ciaran O'ReillySeamas C Donnelly
Jul 15, 2016·Medical Oncology·Lin WangDong-Sheng Pei
Dec 24, 2019·Apoptosis : an International Journal on Programmed Cell Death·Vishal Kumar GuptaAjay Kumar
Feb 23, 2019·International Journal of Molecular Sciences·Youngjin HanYong Sang Song

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Methods Mentioned

BETA
transgenic
ELISA
immunoprecipitation
Assay
co-immunoprecipitation
pull down
confocal microscopy
nuclear translocation
ubiquitination

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