Dated: Jul 07, 2023
Publication Name: Oncogene
Citations : Activation of invasion by oncogenic reprogramming of cholesterol metabolism via increased NPC1 expression and macropinocytosis
Cancer cells are dependent on cholesterol, and they possess strictly controlled cholesterol homeostasis mechanisms. These allow them to smoothly switch between cholesterol synthesis and uptake to fulfill their needs and to adapt environmental changes. Here we describe a mechanism of how cancer cells employ oncogenic growth factor signaling to promote uptake and utilization of extracellular cholesterol via macropinocytosis. The ability to obtain cholesterol as a byproduct of increased macropinocytosis allows cancer cells to direct the resources needed for the energy-consuming cholesterol synthesis towards other activities such as invasion. These results demonstrate that macropinocytosis is not only an alternative energy source for cancer cells but also an efficient way to provide building material, such as cholesterol, for its macromolecules and membranes.
Contributors: Aikaterini Skorda, Anna Røssberg Lauridsen, Chengnan Wu, Jinrong Huang, Monika Mrackova, Nuggi Ingholt Winther, Vanessa Jank, Zsofia Sztupinszki, Robert Strauss, Mesut Bilgin, Kenji Maeda, Bin Liu, Yonglun Luo, Marja Jäättelä & Tuula Kallunki