Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The . gov means it’s official. Federal government websites often end in VSports app下载. gov or . mil. Before sharing sensitive information, make sure you’re on a federal government site. .

Https

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely. V体育官网.

Review
. 2015 Feb;6(2):88-100.
doi: 10.1007/s13238-014-0119-z. Epub 2014 Dec 6.

Iron homeostasis and tumorigenesis: molecular mechanisms and therapeutic opportunities

Caiguo Zhang  1 , Fan Zhang
Affiliations
Review

"VSports注册入口" Iron homeostasis and tumorigenesis: molecular mechanisms and therapeutic opportunities

Caiguo Zhang et al. Protein Cell. 2015 Feb.

"V体育官网" 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. VSports手机版.

PubMed Disclaimer

"V体育2025版" Figures

Figure 1
Figure 1
Iron is implicated in multiple cancer types. These cancers mainly include breast cancer, lung cancer, prostate cancer, pancreatic cancer, melanoma, bladder cancer, hepatocellular cancer, colorectal cancer, gastric cancer and haematological cancers
Figure 2
Figure 2
Cellular iron metabolism in mammals. Apo-Tf binds ferric iron to form holo-Tf. Holo-Tf further forms a complex with TfR1 on the cell surface and the complex undergoes endocytosis. Acidifying by a proton pump, ferric iron is released from holo-Tf in the endosome, where Steap3 reduces ferric iron to ferrous iron. Further, ferrous iron is transported across the endosomal membrane to the cytosol by DMT1. DMT1 also facilitates dietary ferrous iron absorption in the plasma. The released apo-Tf is recycled back to the plasma membrane to repeat another cycle. Newly acquired iron enters into cytosolic “labile iron pool” (LIP) (Pantopoulos et al., 2012). The LIP is utilized by iron-sulfur clusters (Fe-S) proteins, hemoproteins, RNR and other iron-containing proteins, which localize in different cellular compartments (Zhang, 2014). Cellular iron that is not utilized is either stored in ferritin or exported via ferroportin (Pantopoulos et al., 2012)
Figure 3
Figure 3
Iron metabolism in normal cell and cancer cell. (A) The expression of Tf, TfR1, TfR2 and hepcidin is low, whereas the expression of iron exporter gene FPN is high in normal cells, leading to a small pool of labile iron (Torti and Torti, 2013). (B) Cancer cells exhibit increased expression of TfR1 and hepcidin, but low levels of FPN, leading to an increased labile iron pool (Torti and Torti, 2013)
Figure 4
Figure 4
Signal pathways in cancers caused by iron excess. A variety of signal pathways are activated in multiple cancer types. These pathways mainly include p53 pathway, Wnt pathway, HIF pathway, DNA replication and repair pathway, cyclins and cell cycle regulation, and oxidative stress pathways
See this image and copyright information in PMC

References

    1. Al Robaian M, Chiam KY, Blatchford DR, Dufes C. Therapeutic efficacy of intravenously administered transferrin-conjugated dendriplexes on prostate carcinomas. Nanomedicine (Lond) 2014;9:421–434. - PubMed
    1. Aleman MR, Santolaria F, Batista N, de La Vega M, Gonzalez-Reimers E, Milena A, Llanos M, Gomez-Sirvent JL. Leptin role in advanced lung cancer. A mediator of the acute phase response or a marker of the status of nutrition? Cytokine. 2002;19:21–26. - PubMed
    1. Anderson GJ, Vulpe CD. Mammalian iron transport. Cell Mol Life Sci. 2009;66:3241–3261. - PMC - PubMed
    1. Andrews NC, Schmidt PJ. Iron homeostasis. Annu Rev Physiol. 2007;69:69–85. - PubMed
    1. Armaghany T, Wilson JD, Chu Q, Mills G. Genetic alterations in colorectal cancer. Gastrointest Cancer Res. 2012;5:19–27. - "V体育官网" PMC - PubMed

MeSH terms