From obesity to liver cancer: Can we prevent the worst?

February 19, 2020

Hepatocellular carcinoma, a very common liver cancer linked to the presence of fat in the liver, is one of the leading causes of cancer death worldwide. With the increase in our sedentary lifestyle and in the sugar and fat content of our diet, the number of individuals at risk is on the rise. Scientists at the University of Geneva (UNIGE) have discovered a protein involved in the progression of a "fatty liver" towards cancer. This protein, S100A11, could not only allow early detection of the risk of developing liver cancer, but also open the way to new targeted therapies. These results, published in the journal Gut, highlight the close links between our diet and cancer development.

Hepatocellular carcinoma is the most common liver cancer. It can occur in the context of a chronic liver inflammation caused by excessive fat accumulation. Obesity is therefore an important risk factor for the development of this cancer. The difficulty in detecting it and the lack of targeted treatment contribute to the severity of this disease, which causes the death of more than 700,000 people per year worldwide. Moreover, with almost 41% of the Swiss population being overweight or obese, the extent of this cancer is likely to alarmingly increase in the next decades.

When fat triggers liver sickness

Among the largest organs in our body, the liver performs essential functions and is involved in the storage of sugars and fats from food. If the diet is too caloric, liver cells accumulate the excess of energy under the form of fat, a pathological condition called fatty liver disease. Inflammation and build-up of fibrous tissue can then develop and even lead to cirrhosis or cancer. These dysfunctions, initially asymptomatic, often go unnoticed or are considered benign. "We already know that a fatty liver can become inflamed and progress into cancer, but very little is known about the molecular mechanisms responsible for these pathologies", explains Michelangelo Foti, Professor and Director of the Department of Cell Physiology and Metabolism at UNIGE Faculty of Medicine, who supervised this work. "Fatty liver disease already affects nearly 30% of the world's population and will very quickly become a major public health problem."

A protein network involved

The aim of UNIGE researchers was to detect changes in the expression of specific proteins that could promote cancer development. "To date, studies have focused mainly on genetic mutations associated with liver cancer, but this has not led to effective treatments", adds Michelangelo Foti. "That is why we have been looking for other alterations that could explain the progression of a fatty liver towards an inflammatory state and cancer."

It turns out that a whole network of proteins becomes deregulated, in the absence of any genetic alterations, thereby creating an amenable environment to the development of cancer. Among this network, the protein S100A11 particularly caught the attention of scientists. "We first discovered that S100A11 promotes inflammation and build-up of fibrous tissue in the liver", explains Cyril Sobolewski, researcher at the Department of Cell Physiology and Metabolism and first author of this work. "Additional tests showed that the more S100A11 was expressed, the greater the severity of the cancer."

A therapeutic target?

The discrete symptoms of liver inflammation and cancer play an important role in their dangerousness, but the presence of S100A11 in the blood raises the possibility of an early detection by simple blood sampling. "The earlier the patient is treated, the greater the chances of survival", highlights Michelangelo Foti. "In addition, S100A11 may be a promising therapeutic target, says Cyril Sobolewski. The next step would be to generate specific antibodies able to neutralize the protein and prevent its carcinogenic effect." This type of approach, called immunotherapy, has already shown promising results in the fight against several cancers.
-end-


Université de Genève

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.