Role of interleukin-32 in cancer biology

Abstract

Interleukin-32 (IL-32), a novel proinflammatory cytokine, is highly expressed in various cancer tissues and in established cancer cell lines. IL-32 has been revealed to serve a crucial role in human cancer development, including tumour initiation, proliferation and maintenance. The expression of IL-32 is regulated by numerous factors, including genetic variations, hypoxia and acidosis in the tumour microenvironment. Understanding the underlying mechanisms of IL-32 expression and its function are critical for the discovery of novel therapeutic strategies that target IL-32. This is a review of the current literature on the regulation and function of IL-32 in cancer progression, focusing on the molecular pathways linking IL-32 and tumour development.

Keywords: cancer; interleukin-32; mechanisms; regulation.

Figure 1.

The role and molecular pathway of IL-32 in cancer. IL-32 activates 3 pathways: The P38-MAPK, NF-κB/STAT-3 and PI3K/Akt pathways. The activation of these pathways modifies the expression of several genes that affect cell proliferation, survival, migration and invasion, and carcinogenic angiogenesis and inflammation, causing tumorigenic effects. IL, interleukin; MAPK, mitogen-activated protein kinase; NF-κB, nuclear factor-κB; Bcl, B-cell lymphoma; Mcl-1, induced myeloid leukemia cell differentiation protein 1; XIAP, x-linked inhibitor of apoptosis; PUMA, p53 upregulated modulator of apoptosis; MMP, matrix metalloproteinase; VEGF, vascular endothelial growth factor; STAT, signal transducer and activator of transcription; PI3K, phosphoinositide 3-kinase; Akt, protein kinase B; HIF, hypoxia-inducible factor; TNF, tumour necrosis factor.