About My Health Careers Internship MedBlogs Contact us
Medindia LOGIN REGISTER
Advertisement

Keeping A Check On Cancer

by Rukmani Krishna on April 9, 2013 at 12:36 PM
Font : A-A+

 Keeping A Check On Cancer

Did you know that healthy cells don't just happen? They need checks and balances as they grow and divide, to ensure that they function properly while adapting to changing conditions around them.

Researchers studying a set of proteins that regulate physiology, caloric restriction and aging have discovered another important role that one of them plays. SIRT4, one of seven sirtuin proteins, is known for controlling fuel usage from its post in the mitochondria, the cell's energy source. It responds to stressful changes in the availability of nutrients for the cell.

Advertisement

New research reveals that SIRT4 is also extremely sensitive to a different form of stress: DNA damage. This unsuspected response by the metabolic checkpoint means SIRT4 doubles as a sentry guarding against cancer, which is spurred by genetic abnormalities.

Sirtuins have become familiar for their connection to longevity and to resveratrol, the red-wine compound that activates SIRT1, but less attention has been focused on SIRT3, SIRT 4 and SIRT5, all of which are found in mitochondria. Marcia Haigis, HMS associate professor of cell biology, led a team that has uncovered SIRT4 as an important player in the DNA damage response pathway, coordinating a sequence of events that normally result[s] in tumor suppression. They published their results April 4 in Cancer Cell.
Advertisement

"When we started studying SIRT4, we were focused only on its metabolic role, looking for functions related to diabetes and obesity," said Haigis. "What we found, to our surprise, was that SIRT4 was responsive to DNA damage, so that led us to investigate the metabolic response to DNA damage and how SIRT4 controls the metabolic response to genotoxic stress."

To see how SIRT4 normally functions, Haigis and her colleagues induced DNA damage by exposing cells in a lab dish to ultraviolet light. This damage triggered a halt in glutamine metabolism, limiting the amount of nutrients the cell could use as it goes through a cycle of division and growth.

Blocking the cell cycle at this juncture is important. If cell growth after DNA damage goes unchecked, proliferation of impaired cells can lead to cancer. When SIRT4 works properly, this chain of events is broken before bad cells and their abnormal genes multiply. SIRT4 blocks glutamine metabolism, arrests the cell cycle and suppresses tumor formation.

The scientists tested this SIRT4 response in mice. Bred to lack the gene that encodes the SIRT4 protein but otherwise normal, the mice spontaneously developed lung cancer by 15 months.

"When SIRT4 is missing, you don't have this metabolic checkpoint involving glutamine, which is important because glutamine is an amino acid required for proliferation in the cell," Haigis said. "Without SIRT4, the cell keeps dividing even in the face of DNA damage, so the cell accumulates more damage."

The scientists also analyzed data showing SIRT4 gene expression levels are low in several human cancers, including small-cell lung carcinoma, gastric cancer, bladder carcinoma, breast cancer and leukemia.

While they cannot say if SIRT4 loss alone will initiate cancer, its absence appears to create an environment in which tumor cells survive and grow.

"Our findings suggest that SIRT4 may be a potential target against tumors," they conclude.

Source: Eurekalert
Advertisement

Advertisement
News A-Z
A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
Advertisement
News Category
What's New on Medindia
January is the Thyroid Awareness Month in 2022
Menstrual Disorders
Coffee May Help You Fight Endometrial Cancer
View all

Medindia Newsletters Subscribe to our Free Newsletters!
Terms & Conditions and Privacy Policy.

More News on:
Cancer and Homeopathy Cancer Facts Cancer Tattoos A Body Art 

Recommended Reading
Breast Cancer Screening using Mammogram
Breast cancer if detected early can be completely cured. Mammography is used to screen women for ......
Quiz on Breast Cancer
Breast cancer is one of the leading causes of cancer deaths among women. It is often said that a ......
World Cancer Death Clock
World Cancer Death Clock is a dynamic calculator that constantly updates the number of people in ......
Cancer Prevention thro' Lifestyle Changes
Did u know that simple changes in lifestyle could lower your cancer risks? Find out how!...
Tattoos A Body Art
Tattoos are a rage among college students who sport it for the ‘cool dude’ or ‘cool babe’ look...

Disclaimer - All information and content on this site are for information and educational purposes only. The information should not be used for either diagnosis or treatment or both for any health related problem or disease. Always seek the advice of a qualified physician for medical diagnosis and treatment. Full Disclaimer

© All Rights Reserved 1997 - 2022

This site uses cookies to deliver our services. By using our site, you acknowledge that you have read and understand our Cookie Policy, Privacy Policy, and our Terms of Use
open close
ASK A DOCTOR ONLINE
I have read and I do accept terms of use - Telemedicine

Advantage Medindia: FREE subscription for 'Personalised Health & Wellness website with consultation' (Value Rs.300/-)