The Molecular Basis and Therapeutic Potential of Leukemia Inhibitory Factor in Cancer Cachexia.

Abstract

Simple SummaryThe mechanism of cancer cachexia is linked to a variety of factors, and inflammatory factors are thought to play a key role. We summarize the main roles of LIF in the development of cancer cachexia, including promoting fat loss, inducing skeletal muscle atrophy and causing anorexia nervosa. The main aim of this review is to increase the understanding of the effects of LIF in cachexia and to provide new insights into the treatment of cancer cachexia.Cachexia is a chronic metabolic syndrome that is characterized by sustained weight and muscle mass loss and anorexia. Cachexia can be secondary to a variety of diseases and affects the prognosis of patients significantly. The increase in inflammatory cytokines in plasma is deeply related to the occurrence of cachexia. As a member of the IL-6 cytokine family, leukemia inhibitory factor (LIF) exerts multiple biological functions. LIF is over-expressed in the cancer cells and stromal cells of various tumors, promoting the malignant development of tumors via the autocrine and paracrine systems. Intriguingly, increasing studies have confirmed that LIF contributes to the progression of cachexia, especially in patients with metastatic tumors. This review combines all of the evidence to summarize the mechanism of LIF-induced cachexia from the following four aspects: (i) LIF and cancer-associated cachexia, (ii) LIF and alterations of adipose tissue in cachexia, (iii) LIF and anorexia nervosa in cachexia, and (iv) LIF and muscle atrophy in cachexia. Considering the complex mechanisms in cachexia, we also focus on the interactions between LIF and other key cytokines in cachexia and existing therapeutics targeting LIF.