Abstract
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.
Highlights
Leukemia inhibitory factor (LIF) is a multifunction cytokine
Our recent report showed that LIF promotes the invasion and migration of in vitro cultured breast cancer cells and lung metastasis in nude mice injected with breast cancer cells via the tail vein [3]
LIF overexpression is frequently observed in many human tumors, including breast cancer, colorectal cancer, lung cancer, head and neck cancer, melanoma and nasopharyngeal carcinoma
Summary
Leukemia inhibitory factor (LIF) is a multifunction cytokine. LIF functions through an autocrine or paracrine manner to bind to its receptor complex, LIF receptor (LIF-R)/gp130, and leads to the activation of many signaling pathways. In different types of tissues and cells, and different stages of development, LIF activates distinct signaling pathways, including JAK/ STAT3, MAPK, ERK, AKT and mTOR signaling, etc., and is involved in many important biological functions in neuronal, endocrine, reproductive, inflammatory and immune systems [1,2,3,4]. Recent studies including ours have shown that LIF is an important player for the progression and metastasis of different types of solid tumors [3,4,5,6]. LIF is frequently overexpressed in different types of human tumors, including breast cancer, colorectal cancer, nasopharyngeal carcinoma, lung cancer and melanoma [3,4,5,6]. Despite the important role of LIF in tumor metastasis, its underlying mechanism is far from clear
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
