A protein with a dual action in liver cancer

Cancer is the second leading cause of death globally. To date, studies have focused mainly on genetic mutations. This strategy allowed to provide therapeutic options for a wide range of cancers, but has not led to effective treatments for hepatocellular carcinoma, a very common and severe liver cancer.


The hope of AUBPs

Looking for other alterations that could explain the development of this liver cancer, researchers from the laboratory of Prof. Michelangelo Foti have begun to take an interest in some proteins that regulate gene expression, the AUBPs. These AU-rich element-binding proteins play important roles in liver diseases and cancer, and might be potential diagnostic tools and therapeutic targets, as highlighted in their recent review in the International Journal of Molecular Sciences.


The dual action of tristetraprolin

One of these AUBPs, tristetraprolin, had always been reported to act as a tumor suppressor, its loss promoting cancer. In their recent study published in Cellular and Molecular Gastroenterology and Hepatology, scientists from Prof. Foti laboratory discovered that a loss of function of TTP does not necessarily promote cancer, but has two opposite roles. On the one hand, as expected, a loss of tristetraprolin enhances cancer cells migration and invasion. However, on the other hand, TTP loss slows down liver inflammation and cancer initiation.



Tristetraprolin TTP has a dual action. Its loss slows down liver inflammation (NASH and fibrosis) and cancer initiation, but enhances cancer malignancy. © Dolicka et al. 2020, Cellular and Molecular Gastroenterology and Hepatology


What’s next?

This new discovery shakes the dogma of tristetraprolin being a tumor suppressor and calls for a deeper investigation of the AUBP family. Scientists are continuing on this exciting path in order to determine the exact role of these proteins and the environmental factors that are regulating them.

19 Oct 2020