Exploring retrograde trafficking: mechanisms and consequences in cancer and disease

Rachel Bingham, Helen McCarthy, Niamh Buckley*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

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Abstract

Retrograde trafficking (RT) orchestrates the intracellular movement of cargo from the plasma membrane, endosomes, Golgi or endoplasmic reticulum (ER)–Golgi intermediate compartment (ERGIC) in an inward/ER-directed manner. RT works as the opposing movement to anterograde trafficking (outward secretion), and the two work together to maintain cellular homeostasis. This is achieved through maintaining cell polarity, retrieving proteins responsible for anterograde trafficking and redirecting proteins that become mis-localised. However, aberrant RT can alter the correct location of key proteins, and thus inhibit or indeed change their canonical function, potentially causing disease. This review highlights the recent advances in the understanding of how upregulation, downregulation or hijacking of RT impacts the localisation of key proteins in cancer and disease to drive progression. Cargoes impacted by aberrant RT are varied amongst maladies including neurodegenerative diseases, autoimmune diseases, bacterial and viral infections (including SARS-CoV-2), and cancer. As we explore the intricacies of RT, it becomes increasingly apparent that it holds significant potential as a target for future therapies to offer more effective interventions in a wide range of pathological conditions.

Original languageEnglish
Article numbere12931
Number of pages15
JournalTraffic
Volume25
Issue number2
DOIs
Publication statusPublished - Feb 2024

Keywords

  • COPI complex
  • Cell Membrane - metabolism
  • Endoplasmic Reticulum - metabolism
  • Endosomes - metabolism
  • Golgi Apparatus - metabolism
  • Humans
  • Neoplasms - metabolism
  • Protein Transport
  • SARS-CoV-2
  • cancer
  • clathrin
  • receptor tyrosine kinase
  • retrograde trafficking
  • retromer
  • vesicle

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