Exploiting cancer's drinking problem: regulation and therapeutic potential of macropinocytosis.

Joseph Puccini, Michael Alexander Badgley, Dafna Bar-Sagi

Journal: Trends in cancer 2022;8(1):54-64

PMID: 34649835

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Abstract

Macropinocytosis, an evolutionarily conserved endocytic mechanism that mediates non-specific fluid-phase uptake, is potently upregulated by various oncogenic pathways. It is now well appreciated that high macropinocytic activity is a hallmark of many human tumors, which use this adaptation to scavenge extracellular nutrients for fueling cell growth. In the context of the nutrient-scarce tumor microenvironment, this process provides tumor cells with metabolic flexibility. However, dependence on this scavenging mechanism also illuminates a potential metabolic vulnerability. As such, there is a great deal of interest in understanding the molecular underpinnings of macropinocytosis. In this review, we will discuss the most recent advances in characterizing macropinocytosis: the pathways that regulate it, its contribution to the metabolic fitness of cancer cells, and its therapeutic potential.

Address: Department of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, New York, NY, USA.; Department of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, New York, NY, USA. Electronic address: [email protected].

DOI: 10.1016/j.trecan.2021.09.004