Research Papers:

Leukemia inhibitory factor promotes EMT through STAT3-dependent miR-21 induction

Xuetian Yue, Yuhan Zhao, Cen Zhang, Jun Li, Zhen Liu, Juan Liu and Wenwei Hu _

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Oncotarget. 2016; 7:3777-3790. https://doi.org/10.18632/oncotarget.6756

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Xuetian Yue1, Yuhan Zhao1, Cen Zhang1, Jun Li1, Zhen Liu1, Juan Liu1, Wenwei Hu1,2

1Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers State University of New Jersey, New Brunswick, NJ, USA

2Department of Pharmacology, Rutgers State University of New Jersey, New Brunswick, NJ, USA

Correspondence to:

Wenwei Hu, e-mail: [email protected]

Keywords: LIF, miR-21, epithelial-mesenchymal transition, STAT3

Received: September 07, 2015     Accepted: November 26, 2015     Published: December 24, 2015


Leukemia inhibitory factor (LIF) is a multi-function cytokine. Its role in cancer is not well-understood. Recent studies including ours show that LIF is frequently overexpressed in many types of human tumors and promotes the progression and metastasis of tumors. However, the underlying mechanism of LIF’s promoting effects on tumor progression and metastasis is poorly defined. Epithelial-mesenchymal transition (EMT) plays an important role in tumor metastasis. This study reports that LIF promotes EMT in human tumor cells. Overexpression of LIF promotes tumor cells to acquire mesenchymal features, including morphological changes of cells from epithelial-like to mesenchymal-like, increased expression levels of mesenchymal markers and decreased expression of epithelial markers. Knockdown of endogenous LIF reverses EMT in cancer cells. We further identified that LIF induces the expression of microRNA-21 (miR-21), which in turn mediates the promoting effect of LIF on EMT. LIF induces miR-21 expression through the activation of STAT3. Importantly, blocking miR-21 function greatly abolished the promoting effect of LIF on EMT and the migration ability of cancer cells. Taken together, results from this study identified an important function and a novel underlying mechanism of LIF in EMT and tumor metastasis.

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