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

How Whole-body Metabolism Affects Tumor Formation

by Anjali Aryamvally on April 11, 2018 at 12:06 PM
Font : A-A+

How Whole-body Metabolism Affects Tumor Formation

Inactivation of a protein called p62 in fat cells fuels aggressive, metastatic prostate cancer in mice, shows study from Sanford Prebys Medical Discovery Institute (SBP). The study findings are reported in Cancer Cell.

Obesity is the second-leading preventable cause of cancer and represents one of the greatest threats to global human health. But it has not been clear exactly how whole-body metabolism affects tumor formation. In particular, the molecular mechanisms by which fat cells communicate with tumor tissue remain poorly understood.

Advertisement


"This work could lead to better therapies that consider cancer not just as a genetic or cellular disease, but as a whole-body process where tumors communicate with metabolic organs to maintain their unlimited appetite for nutrients," says co-senior study author Maria Diaz-Meco, Ph.D., a professor in the Cancer Metabolism and Signaling Networks Program at SBP. "This is a vulnerability that can be targeted therapeutically."

Diverting energy

Prostate cancer is the second-leading cause of cancer death among men in the United States, and obesity is a major risk factor for the progression and aggressiveness of this disease. But the underlying molecular mechanisms have remained unclear, in part due to the limitations of mouse models of obesity, which have not allowed researchers to study the specific crosstalk between fat cells and tumor tissue independently of dietary factors.
Advertisement

"Most of the studies addressing the role of adiposity and obesity in cancer use mice fed a high-fat diet," says co-senior study author Jorge Moscat, Ph.D., director and professor of the Cancer Metabolism and Signaling Networks Program at SBP. "Although this mimics some of the situations in patients, it prevents a real understanding of the signaling pathways that control the bidirectional communication between tumors and adipocytes, or fat cells. This is essential if we want to identify therapeutic targets that can be harnessed to prevent the pro-tumorigenic signals emanating from the adipose tissue."

To address this problem, Diaz-Meco and Moscat turned to a mouse model of obesity they previously helped to develop. These mice specifically lack p62 in fat cells, leading to increased adiposity and metabolic problems without altering food intake. In the new study, the researchers reveal a central role of p62 in fat tissue-tumor communication, which supports cancer metabolic fitness.

Specifically, they found that p62 deficiency in fat cells promotes the progression and metastasis of prostate cancer in mice by inhibiting a protein complex called mTORC1. The tumors suppress energy-consuming activities such as fat cell development, a metabolic process called oxidative phosphorylation, and fatty acid metabolism in white fat tissue. As a result, more fatty acids and other nutrients are available to support tumor growth. "This metabolic reprograming orchestrated by the loss of p62 in adipocytes appears to help tumors cope with the high-energy demands of an aggressive cancer," Diaz-Meco says.

Additional experiments showed that p62 deficiency in fat tissue promotes the synthesis of proteins called osteopontin and Cpt1a, which are critical for prostate cancer proliferation, migration and invasion. These findings are clinically relevant because high levels of osteopontin and Cpt1a are associated with aggressive, metastatic castration-resistant prostate cancer in humans. "The significance is huge because we identify a new set of therapeutic targets that, if modulated, should block the ability of activated adipose tissue to promote tumor malignancy," Moscat says.

Beyond genetics

According to the authors, the findings suggest that mTOR inhibitors currently used to treat a wide range of cancers may have the unintended consequence of shutting down fat tissue metabolism and fueling tumor growth, at least under certain circumstances. But this possibility needs to be evaluated in future studies. For their own part, the authors plan to further investigate the p62 signaling pathway in patients and identify druggable targets that could be evaluated for their therapeutic potential.

"We need to consider other aspects of cancer therapeutics beyond the better-known genetics," Diaz-Meco says. "That is, we need to invest more in the research of cancer metabolism, which deals with the identification of metabolic vulnerabilities that should be common to all types of cancers. This will ultimately lead to better therapies that are less susceptible to resistance, which is an all-too-common problem in oncogene-target approaches."



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
Turmeric: Magic Ingredient to Keep you Healthy in Winter
Top 7 Benefits of Good Oral Hygiene
Healthy and Safer Thanksgiving 2021
View all

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

More News on:
Tumor Markers For Cancer Diagnosis and Prognosis Resting Metabolic Rate Galactosemia Top 10 Ways to Speed up Your Metabolism For Weight Loss 

Recommended Reading
Binge Eating Reveals Obesity Clues: Animal Study
Hypercaloric food intake promotes behavioural and cognitive changes. Hypercaloric food intake could ...
COBD Explores Decline in Childhood Obesity Rates
Childhood Obesity Declines Project (COBD) analyzes community-based strategies that have led to ......
Obesity Shows Negative Impact on Liver Health in Kids
Obesity can influence fatty liver disease in children due to increase in liver enzyme like ALT , ......
Urban Design may Reduce the Risk of Childhood Obesity
Urban design with pedestrian-friendly amenities helps children to engage in physical activity ......
Galactosemia
Galactosemia is one of many genetically inherited diseases and it affects one’s ability to process g...
Resting Metabolic Rate
Understanding how metabolic process is regulated and what factors affect the same is crucial before ...
Top 10 Ways to Speed up Your Metabolism For Weight Loss
Boosting metabolism is what we need to pump our weight loss regime. Slow body metabolism can be the ...
Tumor Markers For Cancer Diagnosis and Prognosis
An ideal tumor marker for a cancer should be specific to that cancer and not generate false positive...

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 - 2021

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