The Dual Role of Macropinocytosis in Cancers: Promoting Growth and Inducing Methuosis to Participate in Anticancer Therapies as Targets

Abstract

Macropinocytosis is an important mechanism of internalizing extracellular materials and dissolved molecules in eukaryotic cells. Macropinocytosis has a dual effect on cancer cells. On the one hand, cells expressing RAS genes (such as K-RAS, H-RAS) under the stress of nutrient deficiency can spontaneously produce constitutive macropinocytosis to promote the growth of cancer cells by internalization of extracellular nutrients (like proteins), receptors, and extracellular vesicles(EVs). On the other hand, abnormal expression of RAS genes and drug treatment (such as MOMIPP) can induce a novel cell death associated with hyperactivated macropinocytosis: methuosis. Based on the dual effect, there is immense potential for designing anticancer therapies that target macropinocytosis in cancer cells. In view of the fact that there has been little review of the dual effect of macropinocytosis in cancer cells, herein, we systematically review the general process of macropinocytosis, its specific manifestation in cancer cells, and its application in cancer treatment, including anticancer drug delivery and destruction of macropinocytosis. This review aims to serve as a reference for studying macropinocytosis in cancers and designing macropinocytosis-targeting anticancer drugs in the future.

Local Membrane Curvature Pins and Guides Excitable Membrane Waves in Chemotactic and Macropinocytic Cells - Biomedical Insights From an Innovative Simple Model

“…While this pathway is also observed in diverse range of mammalian cells too, such as immune cells, endothelial and epithelial cells (Lin et al, 2020 ), they also play an essential role in cancer cells as reviewed in Ha et al ( 2016 ), Recouvreux and Commisso ( 2017 ), Zhang and Commisso ( 2019 ), and Ritter et al ( 2021 ). It has been identified that macropinocytosis is a mechanism by which cancer cells support their unique metabolic needs (Commisso et al, 2013 ), and has therefore increased the interest for anticancer therapies (Ritter et al, 2021 ; Song et al, 2021 ). The findings presented here open an interesting new aspect to macropinocytosis that suggests relevance to cancer cells too, as PIP3 domain dynamics are observed as self-organizing waves that are prone to be pinned and guided by strongly bended membranes, just as observed during the formation of macropinocytic cups (Veltman et al, 2016 ).…”

From Pinocytosis to Methuosis—Fluid Consumption as a Risk Factor for Cell Death

“…It will be necessary to unravel not only their specific modes of actions but also their harmful effects, as they might be used for a broad variety of applications, e.g., for eco-friendly biological pest control in agriculture to overcome multidrug resistance of parasites ( Bogner et al, 2017 ; Rajasekharan and Lee, 2020 ; Rajasekharan et al, 2020 ). Importantly, they may emerge as new treatment options for various diseases, e.g., cancer ( Song S. et al, 2020 ; Xiao et al, 2021 ), ALS, or dementia ( Fomin et al, 2018 ; Fomin, 2019 ).…”

Synthesis, Self-Assembly and In Vitro Cellular Uptake Kinetics of Nanosized Drug Carriers Based on Aggregates of Amphiphilic Oligomers of N-Vinyl-2-pyrrolidone

“…Although this effect was shown using a model hydrophobic drug-DiI dye, it can be assumed that a similar effect can be observed for other pharmacologically active compounds. This can be particularly important for transiting from systemic application of free drugs, mainly used at the present time, to novel drug delivery systems with encapsulated drugs, in particular, as macropinocytosis is not only involved in supplying the nutrition for cancer cells but is also instrumental in formation of drug resistance of cancer cells [33,41,42].…”