Glycogen overload transforms the liver

Glycogen is a fast and accessible form of energy. Glycogen accumulation occurs when it is synthesized excessively or is not broken down, and it plays an important role in many physiological processes. In addition, the accumulated glycogen may provide nourishment or serve as a mediator in nutrient-poor tumor environments thereby potentiating tumor growth. Liu et al. reveal that accumulated glycogen promotes liver tumor initiation by inhibiting the Hippo signaling pathway. Furthermore, it spontaneously undergoes liquid-liquid phase separation (LLPS). The retention of Mst1/2 in glycogen droplets formed by LLPS subsequently blocks the Hippo pathway, activates YAP and promotes liver tumorigenesis. This study highlights the importance of glycogen accumulation in liver tumorigenesis and expands the drugs targeting accumulated glycogen, which may open a new avenue for the early detection and treatment of liver tumors.