Macropinocytosis: mechanism and targeted therapy in cancers

Macropinocytosis is a form of endocytosis which provides an effective way for non-selective uptakes of extracellular proteins, liquids, and particles. The endocytic process is initiated by the activation of the growth factors signaling pathways. After activation of the biochemical signal, the cell starts internalizing extracellular solutes and nutrients into the irregular endocytic vesicles, known as macropinosomes that deliver them into the lysosomes for degradation. Macropinocytosis plays an important role in the nutritional supply of cancer cells. Due to the rapid expansion of cancer cells and the abnormal vascular microenvironment, cancer cells are usually deprived of oxygen and nutrients. Therefore, they must transform their metabolism to survive and grow in this harsh microenvironment. To satisfy their energy needs, cancer cells enhance the activity of macropinocytosis. Therefore, this metabolic adaptation that is used by cancer cells can be exploited to develop new targeted cancer therapies. In this review, we discuss the molecular mechanism that actuates the process of macropinocytosis in a variety of cancers, and the novel anti-cancer therapeutics in targeting macropinocytosis.