Abstract
Colorectal cancer (CRC) is the third most common cause of cancer-related deaths in industrialized countries. Understanding the mechanisms of growth and progression of CRC is essential to improve treatment. Iron is an essential nutrient for cell growth. Iron overload caused by hereditary mutations or excess dietary iron uptake has been identified as a risk factor for CRC. Intestinal iron is tightly controlled by iron transporters that are responsible for iron uptake, distribution, and export. Dysregulation of intestinal iron transporters are observed in CRC and lead to iron accumulation in tumors. Intratumoral iron results in oxidative stress, lipid peroxidation, protein modification and DNA damage with consequent promotion of oncogene activation. In addition, excess iron in intestinal tumors may lead to increase in tumor-elicited inflammation and tumor growth. Limiting intratumoral iron through specifically chelating excess intestinal iron or modulating activities of iron transporter may be an attractive therapeutic target for CRC.
Highlights
Colorectal cancer (CRC) is the third most common cancer in both men and women, and is the second leading cause of cancer death in the United States [1]
The expression of proteins associated with cellular iron uptake machinery such as DMT-1 and TfR1 is up-regulated in CRC, whereas the expression of the iron export proteins such as FPN and HEPH is decreased in advanced CRC [38] (Figure 1)
Systemic iron levels and local increase in iron accumulation in tumors significantly impacts the progression of CRC
Summary
Colorectal cancer (CRC) is the third most common cancer in both men and women, and is the second leading cause of cancer death in the United States [1]. Each year about 150,000 new cases will be Nutrients 2013, 5 diagnosed in the United States [1], in European countries it is significantly higher, with the expected cases to be over 400,000 per year [2,3]. Understanding the precise mechanisms that are critical in the progression of colon carcinogenesis may provide better treatment strategies for CRC. The etiological factors and molecular mechanisms underlying the pathogenesis of CRC are multifactorial and complex [5]. In addition to inherited mutations and environmental interactions, dietary nutrients play a key role in the development of CRC [6]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
