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. 2019 Jun;5(6):332-334.
doi: 10.1016/j.trecan.2019.04.002. Epub 2019 May 9.

Macropinocytosis in Cancer: A Complex Signaling Network

Yijuan Zhang  1 , Cosimo Commisso  2
Affiliations

Macropinocytosis in Cancer: A Complex Signaling Network

Yijuan Zhang et al. Trends Cancer. 2019 Jun.

Abstract

Macropinocytosis is an important nutrient-scavenging pathway in numerous cancer types, including pancreatic, lung, prostate, and bladder. This Forum highlights recent work identifying the key regulators of macropinocytosis that support tumor cell fitness in different contexts, providing a unique framework for strategies to target macropinocytosis in the treatment of cancer.

Keywords: AMPK; PTEN; Ras; Wnt; integrin αvβ3; macropinocytosis; metabolism.

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Figures

Figure 1.
Figure 1.. The Complex Signaling Network Driving Macropinocytosis in Cancer.
Context-specific key drivers of macropinocytosis have been identified in multiple cancer types. The activation of the Ras pathway, by oncogenic mutation, integrin nanoclustering, or receptor tyrosine kinases, including EGFR and PDGFR, activates downstream effectors such as PI3K, Rac1, and Pak, which are well-known modulators of macropinocytosis. PTEN loss and activation of AMPK can activate PI3K and Rac1 to trigger macropinocytosis in a KRas-independent manner. In addition, the activation of Frizzled (Fz) and LRP5/6 receptors activates the canonical Wnt pathway through inducing the accumulation and nuclear translocation of β-catenin, which in turn activates Pak in a transcription-dependent manner.
See this image and copyright information in PMC

References

    1. Commisso C et al. (2013) Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells. Nature 497, 633–637 - PMC - PubMed
    1. Recouvreux MV and Commisso C (2017) Macropinocytosis: a metabolic adaptation to nutrient stress in cancer. Front. Endocrinol. (Lausanne) 8, 261. - PMC - PubMed
    1. Palm W et al. (2015) The utilization of extracellular proteins as nutrients is suppressed by mTORC1. Cell 162, 259–270 - PMC - PubMed
    1. Kim SM et al. (2018) PTEN deficiency and AMPK activation promote nutrient scavenging and anabolism in prostate cancer cells. Cancer Discov 8, 866–883 - PMC - PubMed
    1. Veithen A et al. (1996) v-Src induces constitutive macropinocytosis in rat fibroblasts. J. Cell Sci 109, 2005–2012 - PubMed

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