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Updated: Apr 12, 2026

Automated Imaging and Analysis for the Quantification of Fluorescently Labeled Macropinosomes
11:01

Automated Imaging and Analysis for the Quantification of Fluorescently Labeled Macropinosomes

Published on: August 24, 2021

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RAB7 counteracts PI3K-driven macropinocytosis activated at early stages of melanoma development

Direna Alonso-Curbelo1,2, Lisa Osterloh1, Estela Cañón1

  • 1Melanoma Laboratory, Molecular Oncology Programme, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.

Oncotarget
|May 27, 2015
PubMed

Insights

Melanoma cells hijack Class I PI3K to drive macropinocytosis, a process counteracted by RAB7-mediated lysosomal degradation. This RAB7 dependency suppresses oncogene-induced senescence, highlighting its role in melanoma progression.

Area of Science:

  • Oncology
  • Cell Biology
  • Melanoma Research

Background:

  • Derailed endolysosomal trafficking is common in aggressive cancers, but the driving oncogenic signals and their role in cancer progression are unclear.
  • Melanoma exhibits significant heterogeneity but uniformly overexpresses endolysosomal genes, showing addiction to the membrane traffic regulator RAB7.

Purpose of the Study:

  • To investigate the upstream drivers and downstream regulators of aberrant vesicular trafficking in melanoma.
  • To define the mechanisms and temporal aspects of melanoma's dependency on RAB7.

Main Methods:

  • Combined electron microscopy, real-time imaging, and mechanistic analyses of vesicular trafficking in normal and malignant human melanocytic cells.
  • Utilized in vitro gain- and loss-of-function studies.
  • Performed histopathological validation in clinical biopsies and genetically-engineered mouse models.

Main Results:

  • Identified Class I PI3K as the trigger for hyperactive macropinosome influx in melanoma cells.
  • Demonstrated that melanoma cells counteract macropinosome influx via RAB7-mediated lysosomal degradation.
  • Showed RAB7 is required to suppress premature cellular senescence induced by PI3K-activating oncogenes.

Conclusions:

  • Class I PI3K and RAB7 play critical roles in regulating endolysosomal trafficking and membrane homeostasis in melanoma.
  • RAB7's function in suppressing oncogene-induced senescence is crucial for melanoma development.
  • Findings provide new insights into RAB7's regulation and function, emphasizing endosomal fitness in melanoma pathogenesis.
Keywords:
endosomesmacropinocytosisoncogene-induced senescenceoncogenic stresssmall GTPases

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