PMID: 25726527Mar 3, 2015Paper

HIF-2α mediates hypoxia-induced LIF expression in human colorectal cancer cells

Oncotarget
Lihua WuWenwei Hu

Abstract

Leukemia inhibitory factor (LIF), a multi-functional cytokine, has a complex role in cancer. While LIF induces the differentiation of several myeloid leukemia cells and inhibits their growth, it also promotes tumor progression, metastasis and chemoresistance in many solid tumors. LIF is frequently overexpressed in a variety of human tumors and its overexpression is often associated with poor prognosis of patients. Currently, the mechanism for LIF overexpression in tumor cells is not well-understood. Here, we report that hypoxia, a hallmark of solid tumors, induced LIF mRNA expression in human colorectal cancer cells. Analysis of LIF promoter revealed several hypoxia-responsive elements (HREs) that can specifically interact with and be transactivated by HIF-2α but not HIF-1α. Consistently, ectopic expression of HIF-2α but not HIF-1α transcriptionally induced LIF expression levels in cells. Knockdown of endogenous HIF-2α but not HIF-1α by siRNA largely abolished the induction of LIF by hypoxia in cells. Furthermore, there is a strong association of HIF-2α overexpression with LIF overexpression in human colorectal cancer specimens. In summary, results from this study demonstrate that hypoxia induces LIF expression in human cancer ...Continue Reading

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Citations

Aug 27, 2015·International Journal of Molecular Sciences·Jun WangZhen-Ning Wang
Nov 2, 2018·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Dina SabryMahmoud A F Khalil
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Dec 2, 2020·Pharmacology & Therapeutics·Cen ZhangZhaohui Feng
Jul 13, 2021·Frontiers in Physiology·Tamara PircherMaximilian Michael Saller
Jul 31, 2021·Journal of Experimental & Clinical Cancer Research : CR·Daniel Otero-Albiol, Amancio Carnero
Aug 17, 2021·Frontiers in Oncology·Joe ChristiansonCheryl L Jorcyk

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