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Cited by 237Cellular transport and secretionAutophagy in Disease and TherapyCancer, Hypoxia, and Metabolism

Macropinocytosis: A Metabolic Adaptation to Nutrient Stress in Cancer

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Recouvreux, Maria Victoria, Commisso, Cosimo·2017·Frontiers in Endocrinology
DOI 10.3389/fendo.2017.00261PMC PMC5649207
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Abstract

Oncogenic mutations, such as Ras mutations, drive not only enhanced proliferation, but also the metabolic adaptations that confer to cancer cells the ability to sustain cell growth in a harsh tumor microenvironment. These adaptations might represent metabolic vulnerabilities that can be exploited to develop novel and more efficient cancer therapies. Macropinocytosis is an evolutionarily conserved endocytic pathway that permits the internalization of extracellular fluid via large endocytic vesicles known as macropinosomes. Recently, macropinocytosis has been determined to function as a nutrient-scavenging pathway in Ras-driven cancer cells. Macropinocytic uptake of extracellular proteins, and their further degradation within endolysosomes, provides the much-needed amino acids that fuel cancer cell metabolism and tumor growth. We review here the molecular mechanisms that govern the process of macropinocytosis, as well as discuss recent work that provides evidence of the important role of macropinocytosis as a nutrient supply pathway in cancer cells.

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  • Macropinocytosis pathway can facilitate internalization of essential molecules, such as ATP, to mediate cancer cell proliferation and survival.

    “Macropinocytosis pathway can also facilitate the internalization of essential molecules, such as ATP, to mediate cancer cell proliferation and survival [122].”

    From Insights of Endocytosis Signaling in Health and Disease (2023) · cites this paper as [122]

    In “Macropinocytosis as a Survival Strategy in Tumors,” the paper reports that KRAS-mutant A549 lung cancer cells take up extracellular ATP through macropinocytosis, increasing their intracellular ATP pool. The section links macropinocytic nutrient uptake to tumor growth, but does not establish that ATP uptake itself promotes cancer-cell proliferation or survival. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

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References 73 · Cited by 237

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Authors
Recouvreux, M. V., & Commisso, C.
Affiliations
Sanford Burnham Prebys Medical Discovery Institute (US)
Corresponding author
Commisso, Cosimo
ORCID
Commisso, Cosimo
Venue
Frontiers in Endocrinology
Publisher
Frontiers Media SA
Published
2017-09-29
Volume
8
Pages
261-261
ISSN
1664-2392 (ISSN-L)
DOI
10.3389/fendo.2017.00261
PMC
PMC5649207
OpenAlex
W2759290374
Cited by
237
References
73
Citations by year
2026: 30 · 2025: 19 · 2024: 18 · 2023: 25 · 2022: 28 · 2021: 46 · 2020: 30 · 2019: 27 · 2018: 14
FWCI
2.26
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Endocrinology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Cancer Institute (R01CA207189)
  • Pancreatic Cancer Action Network (15-20-25-COMM)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Keywords
macropinocytosis, nutritional stress, cancer metabolism, macropinosomes, amino acid uptake, endolysosomal degradation, tumor microenvironment, metabolic vulnerability, cancer therapy

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