Opposing S100 protein functions in liver cancer
Fatty liver disease affects a growing part of the global population, and in some cases can progress to hepatocellular carcinoma, a deadly liver cancer. Proteins of the S100 family have long been considered to promote cancer, but the specific contributions of individual proteins have remained unclear.
Two closely related S100 proteins with opposite effects
Using mouse models, researchers in the laboratory of Obesity, liver metabolic disorders & cancer downregulated two S100 proteins, S100A10 and S100A11. The results showed that a loss of S100A11 reduced the development of liver cancer (as visible in the Figure below), confirming its oncogenic role. However, the absence of S100A10 surprisingly promoted cancer, suggesting that S100A10 may have a protective effect rather than being deleterious.
Compared to the control condition (left panel), the loss of S100A11 reduced the development of liver tumors, in blue (middle panel), whereas the loss of S100A10 promoted cancer progression (right panel). Adapted from the Figure 3 in Delangre et al. 2025 Cell Death & Disease.
Molecular contrasts reflecting physiological complexity
The opposite effects of S100A10 and S100A11 demonstrate that subtle molecular differences can have profound consequences for disease progression. This duality not only deepens our understanding of fatty liver disease and hepatocellular carcinoma but also highlights the need for precise therapeutic approaches that account for such complex biological balances.