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

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TRENDS IN CANCER
卷 8, 期 1, 页码 54-64

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CELL PRESS
DOI: 10.1016/j.trecan.2021.09.004

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  1. National Institutes of Health (NIH)/National Cancer Institute Grant [CA210263]
  2. National Health and Medical Research Council (NHMRC) CJ Martin Biomedical Fellowship [APP1106545]
  3. NIH/NCI [T32CA009161]

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This review discusses the recent advances in understanding macropinocytosis, including its regulatory pathways, its contribution to the metabolic fitness of cancer cells, and its therapeutic potential.
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 micro environment, 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.

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