SLC3A2/CD98hc, autophagy and tumor radioresistance: a link confirmed

David Digomann1, Annett Linge1,2,3,4,5,6, Anna Dubrovska1,2,3,7

  • 1OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf , Dresden , Germany.

Autophagy
|July 6, 2019
PubMed

Insights

Low SLC3A2 expression in head and neck cancers enhances autophagy, increasing tumor radioresistance. Inhibiting autophagy alongside SLC3A2-targeted therapy may improve HNSCC radiosensitization.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • SLC3A2/CD98hc is implicated in amino acid transport, mTOR signaling, and autophagy.
  • SLC3A2 has a known tumorigenic role in various cancers, including head and neck squamous cell carcinomas (HNSCC).
  • The interplay between SLC3A2, autophagy, and radioresistance in HNSCC was previously unclear.

Purpose of the Study:

  • To investigate the role of SLC3A2 in HNSCC radioresistance.
  • To explore the relationship between SLC3A2 expression, autophagy, and patient prognosis.
  • To evaluate SLC3A2 and autophagy inhibition as a potential radiosensitization strategy for HNSCC.

Main Methods:

  • Analysis of SLC3A2 and SLC7A5/LAT1 protein expression in HNSCC patients treated with radiochemotherapy.
  • Assessment of radiosensitivity and autophagy levels in SLC3A2-deficient HNSCC cells.
  • Inhibition of autophagy in SLC3A2 knockout cells using ATG5 knockdown or bafilomycin A1 treatment.

Main Results:

  • Low SLC3A2 and SLC7A5/LAT1 expression correlated with favorable prognosis in locally advanced HNSCC.
  • SLC3A2-deficient HNSCC cells exhibited increased radiosensitivity and heightened autophagy.
  • Autophagy activation serves as a survival mechanism against nutrient stress and radiation damage.
  • Autophagy inhibition (ATG5 knockdown, bafilomycin A1) sensitized SLC3A2-deficient cells to radiation.
  • ATG5 expression levels correlated with overall survival in HNSCC patients.

Conclusions:

  • SLC3A2 deficiency in HNSCC leads to increased autophagy and radiosensitivity.
  • Autophagy acts as a survival mechanism in HNSCC under nutrient stress and radiation.
  • Combined SLC3A2-targeted therapy and autophagy inhibition presents a promising strategy for HNSCC radiosensitization.

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