Regulation of the Hippo Pathway by Phosphatidic Acid-Mediated Lipid-Protein Interaction.

The Hippo pathway plays a crucial role in organ size control and tumor suppression, but its precise regulation is not fully understood. In this study, we discovered that phosphatidic acid (PA)-related lipid signaling is a key regulator of the Hippo pathway. Supplementing PA in various Hippo-activating conditions activates YAP. This PA-related lipid signaling is involved in Rho-mediated YAP activation. Mechanistically, PA directly interacts with Hippo components LATS and NF2 to disrupt LATS-MOB1 complex formation and NF2-mediated LATS membrane translocation and activation, respectively. Inhibition of phospholipase D (PLD)-dependent PA production suppresses YAP oncogenic activities. PLD1 is highly expressed in breast cancer and positively correlates with YAP activation, suggesting their pathological relevance in breast cancer development. Taken together, our study not only reveals a role of PLD-PA lipid signaling in regulating the Hippo pathway but also indicates that the PLD-PA-YAP axis is a potential therapeutic target for cancer treatment.

Relapse of Graves' disease 23 years after treatment with radioactive iodine (131I).

The use of radioactive iodine (131I) in the treatment of Graves' disease results frequently in hypothyroidism requiring thyroid hormone supplementation. Relapse of Graves' disease months after inadequate treatment with 131I is well-recognized. However, late relapse of Graves' disease in a patient rendered hypothyroid by 131I years after therapy has not been reported. The authors discuss a patient who had a relapse of his Graves' disease 23 yr after treatment with 131I. Over the interval the patient had been on 1-thyroxine replacement for hypothyroidism and had persistently high levels of long acting thyroid stimulator or thyroid stimulating antibody. The authors speculate that the immune nature of Graves' disease may play a role in the observed clinical response to 131I.