Leukemia inhibitory factor, a double-edged sword with therapeutic implications in human diseases

Jianming Wang, Chun Yuan Chang, Xue Yang, Fan Zhou, Juan Liu, Zhaohui Feng, Wenwei Hu

Research output: Contribution to journalReview articlepeer-review

7 Scopus citations

Abstract

Leukemia inhibitory factor (LIF) is a pleiotropic cytokine of the interleukin-6 (IL-6) superfamily. LIF was initially discovered as a factor to induce the differentiation of myeloid leukemia cells and thus inhibit their proliferation. Subsequent studies have highlighted the multi-functions of LIF under a wide variety of physiological and pathological conditions in a highly cell-, tissue-, and context-dependent manner. Emerging evidence has demonstrated that LIF plays an essential role in the stem cell niche, where it maintains the homeostasis and regeneration of multiple somatic tissues, including intestine, neuron, and muscle. Further, LIF exerts a crucial regulatory role in immunity and functions as a protective factor against many immunopathological diseases, such as infection, inflammatory bowel disease (IBD), and graft-verse-host disease (GVHD). It is worth noting that while LIF displays a tumor-suppressive function in leukemia, recent studies have highlighted the oncogenic role of LIF in many types of solid tumors, further demonstrating the complexities and context-dependent effects of LIF. In this review, we summarize the recent insights into the roles and mechanisms of LIF in stem cell homeostasis and regeneration, immunity, and cancer, and discuss the potential therapeutic options for human diseases by modulating LIF levels and functions.

Original languageEnglish (US)
Pages (from-to)331-343
Number of pages13
JournalMolecular Therapy
Volume31
Issue number2
DOIs
StatePublished - Feb 1 2023

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

Keywords

  • cancer
  • immunity
  • leukemia inhibitory factor
  • stem cell
  • therapy

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