The Role and Therapeutic Potential of Macropinocytosis in Cancer

Abstract

Macropinocytosis, a unique endocytosis pathway characterized by nonspecific internalization, has a vital role in the uptake of extracellular substances and antigen presentation. It is known to have dual effects on cancer cells, depending on cancer type and certain microenvironmental conditions. It helps cancer cells survive in nutrient-deficient environments, enhances resistance to anticancer drugs, and promotes invasion and metastasis. Conversely, overexpression of the RAS gene alongside drug treatment can lead to methuosis, a novel mode of cell death. The survival and proliferation of cancer cells is closely related to macropinocytosis in the tumor microenvironment (TME), but identifying how these cells interface with the TME is crucial for creating drugs that can limit cancer progression and metastasis. Substantial progress has been made in recent years on designing anticancer therapies that utilize the effects of macropinocytosis. Both the induction and inhibition of macropinocytosis are useful strategies for combating cancer cells. This article systematically reviews the general mechanisms of macropinocytosis, its specific functions in tumor cells, its occurrence in nontumor cells in the TME, and its application in tumor therapies. The aim is to elucidate the role and therapeutic potential of macropinocytosis in cancer treatment.

Compromised osteogenic effect of exosomes internalized by senescent bone marrow stem cells via endocytoses involving clathrin, macropinocytosis and caveolae

“… Li and Pang 2021 ), and such vigorous plasma membrane activity might be hijacked by pathogens for infectious cell entry ( Mercer and Helenius 2009 ). Hyperstimulation of macropinocytosis by active RAS expression or some medicines can cause cell death, also known as methuosis ( Qiu et al, 2022 ). In some cases, macropinocytosis allowed cancer cells to develop resistance to antitumor drug therapies and reduced the drug efficiencies ( Stow, Hung, and Wall 2020 ).…”

Progress in the discovery and development of small molecule methuosis inducers

“…chemical stimuli) factors will result in abnormal cell death (methuosis). 11,12 In recent years, there has been a significant increase in reports on the correlation of mocropinocytosis with tumorgenesis, revealing its important role in the growth, proliferation and drug resistance of a number of tumor cells. Meanwhile with increasing understanding toward this interesting biological process, methuosis caused by macropinocytosis has been gradually recognized as a new promising target for cancer prevention.…”

GTPase-activating protein ARAP1 regulates circular dorsal ruffles as a nutrient uptake mechanism in the Hep3B hepatocellular carcinoma cell line

“…Furthermore, we have recently found that growth factor treatment can induce CDRs in the human Hep3B HCC cell line, although not in other HCC cell lines, such as HepG2 and Huh7, or the LO2 hepatocyte cell line (Sun et al, 2022). Given that macropinocytosis functions in the uptake of extracellular solutes, it has been proposed that heightened nutrient uptake via macropinocytosis in cancer cells triggers sufficient cell growth resulting in tumor development (Yoshida et al, 2018a; Swanson and Yoshida, 2019; Qiu et al, 2022; Puccini et al, 2022). On the basis of these findings, we hypothesized that the development of CDRs in cancer cells is associated with abnormally high levels of macropinocytosis, thereby contributing to the uptake of excess amounts of nutrients and thus promoting rampant tumor growth (Sun et al, 2022).…”