Iron homeostasis and tumorigenesis: molecular mechanisms and therapeutic opportunities.

Caiguo Zhang,Fan Zhang

doi:10.1007/s13238-014-0119-z

Abstract

Excess iron is tightly associated with tumorigenesis in multiple human cancer types through a variety of mechanisms including catalyzing the formation of mutagenic hydroxyl radicals, regulating DNA replication, repair and cell cycle progression, affecting signal transduction in cancer cells, and acting as an essential nutrient for proliferating tumor cells. Thus, multiple therapeutic strategies based on iron deprivation have been developed in cancer therapy. During the past few years, our understanding of genetic association and molecular mechanisms between iron and tumorigenesis has expanded enormously. In this review, we briefly summarize iron homeostasis in mammals, and discuss recent progresses in understanding the aberrant iron metabolism in numerous cancer types, with a focus on studies revealing altered signal transduction in cancer cells.

Highlights

OVERVIEW OF IRON AND CANCERIron serves important functions for mammalian cells as it is involved in cell proliferation, metabolism and growth (Torti and Torti, 2013)
Excess iron is tightly associated with tumorigenesis in multiple human cancer types through a variety of mechanisms including catalyzing the formation of mutagenic hydroxyl radicals, regulating DNA replication, repair and cell cycle progression, affecting signal transduction in cancer cells, and acting as an essential nutrient for proliferating tumor cells
We briefly summarize iron homeostasis in mammals, and discuss recent progresses in understanding the aberrant iron metabolism in numerous cancer types, with a focus on studies revealing altered signal transduction in cancer cells

Summary

INTRODUCTION

Iron serves important functions for mammalian cells as it is involved in cell proliferation, metabolism and growth (Torti and Torti, 2013). Hepcidin expression is increased in tumor tissue and serum of NSCLC patients, and the increased serum hepcidin level is associated with lymph node metastasis and tumor clinical stage of NSCLC (Xiong et al, 2014) Iron related proteins, such as TfR1, H and L subunits of ferritin protein, exhibit increased levels in lung cancer. The tetracycline-inducible overexpression of IRP1 or IRP1C437S mutant results in misregulation of iron metabolism, highly active in IRE-binding and increased TfR1 levels in human H1299 lung cancer cells (Wang and Pantopoulos, 2002), but not altering the growth properties of the H1299 cells in vitro (Wang and Pantopoulos, 2002).

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CONCLUSION

COMPLIANCE WITH ETHICS GUIDELINES