HomeScience and ResearchScientific ResearchScientists Find A New Way To Treat NASH-induced Cancer

Scientists Find A New Way To Treat NASH-induced Cancer

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In nonalcoholic steatohepatitis-associated liver cancer, the formation of cell membrane pores is a key mechanism through which cancer-inducing proteins are released and speed up tumor development.

Do you really need another excuse to refrain from eating that extra side of fries? It might increase the risk of getting liver cancer. Nonalcoholic steatohepatitis (NASH), a form of fatty liver disease that can also result in cancer, is becoming more common, yet there is no cure.

Scientists Find A New Way To Treat NASH-induced Cancer
Scientists Find A New Way To Treat NASH-induced Cancer

With their study using obese mice that explains the significance of secreted proteins from cell membrane pores formed in cells in the vicinity of cancer cells in the tumor microenvironment for cancer development, a research team led by Osaka Metropolitan University took a potential step toward suppression and treatment of NASH-associated liver cancer.

The results of their study were reported in Science Immunology.

While cancer cells by themselves are undoubtedly harmful, nearby cells, such as cancer-associated fibroblasts in a so-called “tumor microenvironment,” can also contribute to the growth of cancer.

The fibroblasts known as “hepatic stellate cells” become senescent in the microenvironment of the obesity-associated liver tumor, according to the study’s principal investigator Professor Naoko Ohtani.

“This causes them to exhibit a senescence-associated secretory phenotype (SASP), where they release a set of proteins that promote cancer by suppressing anti-tumor immunity.” 

It is not well understood how proteins like SASP factors are able to speed up tumor development after they are released.

The release mechanism of SASP factors from hepatic stellate cells and their tumorigenic orchestration. Image Credit: Osaka Metropolitan University

By giving a high-fat diet to mice predisposed to cancer and examining the obesity-induced liver cancer, Professor Ohtani’s team tried to understand this mechanism. They initially carried out a thorough gene expression investigation to identify the SASP components produced by hepatic stellate cells, and then they looked into their release.

IL-1β and IL-33, two SASP factors, were found to be critical drivers of liver cancer growth. There are two key phases to their release.

As explained by Professor:

“First, the high-fat diet weakens gut barrier function, resulting in the migration and accumulation of lipoteichoic acid in the liver.” 

“Second, the accumulated lipoteichoic acid stimulates the cleavage of gasdermin D protein. This, in turn, forms cell membrane pores where IL-1β and IL-33 are exported or released from hepatic stellate cells.”

These pores are essential because, once IL-33 is released, it activates regulatory T cells that are positive for its receptor, which suppresses the immune response to cancer cells and may increase the development of cancer.

Understanding this process is a big step forward in the fight against cancer. Professor Ohtani’s findings “revealed a very interesting mechanism by which the tumor-promoting SASP factors are released through the cell membrane pores formed by the stimulation of gut microbial component.”

“Inhibiting this pore formation may facilitate prevention and therapeutic strategies for NASH-associated liver cancer patients,” the professor concluded.

Image Credit: Getty

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