TY - JOUR
T1 - Leukemia inhibitory factor, a double-edged sword with therapeutic implications in human diseases
AU - Wang, Jianming
AU - Chang, Chun Yuan
AU - Yang, Xue
AU - Zhou, Fan
AU - Liu, Juan
AU - Feng, Zhaohui
AU - Hu, Wenwei
N1 - Publisher Copyright: © 2022 The American Society of Gene and Cell Therapy
PY - 2023/2/1
Y1 - 2023/2/1
N2 - 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.
AB - 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.
KW - cancer
KW - immunity
KW - leukemia inhibitory factor
KW - stem cell
KW - therapy
UR - http://www.scopus.com/inward/record.url?scp=85146327740&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85146327740&partnerID=8YFLogxK
U2 - 10.1016/j.ymthe.2022.12.016
DO - 10.1016/j.ymthe.2022.12.016
M3 - Review article
C2 - 36575793
SN - 1525-0016
VL - 31
SP - 331
EP - 343
JO - Molecular Therapy
JF - Molecular Therapy
IS - 2
ER -