Atypical Macropinocytosis Contributes to Malignant Progression: A Review of Recent Evidence in Endometrioid Endometrial Cancer Cells

Simple Summary A novel type of macropinocytosis has been identified as a trigger for the malignant progression of endometrial cancer. Transiently reducing epithelial barrier homeostasis leads to macropinocytosis by splitting between adjacent cells in endometrioid endometrial cancer. Macropinocytosis causes morphological changes in well-differentiated to poorly differentiated cancer cells. Inhibition of macropinocytosis promotes a persistent dormant state in the intrinsic KRAS-mutated cancer cell line Sawano. This review focuses on the mechanisms of atypical macropinocytosis and its effects on cellular function, and it describes the physiological processes involved in inducing resting conditions in endometrioid endometrial cancer cells. Macropinocytosis is an essential mechanism for the non-specific uptake of extracellular fluids and solutes. In recent years, additional functions have been identified in macropinocytosis, such as the intracellular introduction pathway of drugs, bacterial and viral infection pathways, and nutritional supplement pathway of cancer cells. However, little is known about the changes in cell function after macropinocytosis. Recently, it has been reported that macropinocytosis is essential for endometrial cancer cells to initiate malignant progression in a dormant state. Macropinocytosis is formed by a temporary split of adjacent bicellular junctions of epithelial sheets, rather than from the apical surface or basal membrane, as a result of the transient reduction of tight junction homeostasis. This novel type of macropinocytosis has been suggested to be associated with the malignant pathology of endometriosis and endometrioid endometrial carcinoma. This review outlines the induction of malignant progression of endometrial cancer cells by macropinocytosis based on a new mechanism and the potential preventive mechanism of its malignant progression.

Automated summary

A novel type of macropinocytosis has been identified as a trigger for the malignant progression of endometrial cancer. Inhibition of macropinocytosis promotes a persistent dormant state in cancer cells. This review focuses on the mechanisms of atypical macropinocytosis and its effects on cellular function.