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Updated: Jan 31, 2026

Determining Cell-surface Expression and Endocytic Rate of Proteins in Primary Astrocyte Cultures Using Biotinylation
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Modulation of RAB7A Protein Expression Determines Resistance to Cisplatin through Late Endocytic Pathway Impairment

Flora Guerra1, Aurora Paiano2, Danilo Migoni3

  • 1Department of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, Via Provinciale Lecce-Monteroni 165, 73100 Lecce, Italy. guerraflora@gmail.com.

Cancers
|January 11, 2019
PubMed
Abstract

Insights

Researchers found that RAB7A protein levels impact cisplatin resistance in cancer. Lower RAB7A increases resistance, while higher levels decrease it, affecting drug accumulation and efflux via extracellular vesicles.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Medicine

Background:

  • Cisplatin (CDDP) is a cornerstone chemotherapy agent, but acquired resistance frequently leads to treatment failure.
  • Altered endocytosis and lysosomal function are observed in CDDP-resistant cells, yet their underlying mechanisms remain elusive.

Purpose of the Study:

  • To elucidate the role of RAB7A, a key regulator of late endocytic trafficking, in the development of CDDP resistance.
  • To investigate the relationship between RAB7A expression, endocytic pathway function, and CDDP sensitivity.

Main Methods:

  • Comparative analysis of RAB7A expression in CDDP-resistant and sensitive cells using western blotting, confocal microscopy, and qRT-PCR.
  • Functional studies involving RAB7A modulation via transfection and RNA interference to assess CDDP sensitivity and intracellular drug accumulation.
  • Analysis of extracellular vesicle production and characterization in relation to RAB7A levels.

Main Results:

  • Down-regulation of RAB7A was identified as a hallmark of the CDDP-resistant phenotype.
  • RAB7A depletion significantly enhanced CDDP resistance, whereas RAB7A overexpression conferred increased sensitivity.
  • RAB7A expression levels inversely correlated with CDDP intracellular accumulation and modulated extracellular vesicle production.

Conclusions:

  • RAB7A plays a critical regulatory role in CDDP resistance by influencing late endocytic trafficking.
  • Altered drug efflux mediated by extracellular vesicles, influenced by RAB7A, contributes to CDDP resistance.
  • Targeting RAB7A may offer a novel therapeutic strategy to overcome CDDP resistance in cancer patients.
Keywords:
RAB7Achemoresistancecisplatinendocytosislysosome

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