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Resistance to radiation enhances metastasis by altering RNA metabolism

Ayush Kumar1, Kensei Kishimoto1, Hira L Goel1

  • 1Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.

Science Advances
|October 17, 2025
PubMed

Insights

Radiation resistance in triple-negative breast cancer cells enhances their metastatic capacity by increasing integrin β3 (ITGB3) expression. This process involves RNA metabolism changes mediated by heterogeneous nuclear ribonucleoprotein L (HNRNPL).

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Therapy resistance is linked to cancer metastasis, but the connection between radiation resistance and metastasis is not well understood.
  • Triple-negative breast cancer (TNBC) is an aggressive subtype requiring better treatment strategies.

Purpose of the Study:

  • To investigate the causal link between radiation therapy resistance and metastasis in triple-negative breast cancer.
  • To elucidate the molecular mechanisms driving radiation-induced metastasis.

Main Methods:

  • Investigated radiation-resistant TNBC cells for metastatic potential.
  • Analyzed gene expression changes, focusing on integrin β3 (ITGB3).
  • Utilized bioinformatic analysis and RNA metabolism pathway investigation, including RNA binding proteins and microRNAs.

Main Results:

  • Radiation-resistant TNBC cells exhibit increased migration and invasion.
  • Radiation resistance upregulates integrin β3 (ITGB3) expression.
  • RNA metabolism pathways, specifically heterogeneous nuclear ribonucleoprotein L (HNRNPL)-mediated circular RNA formation, stabilize ITGB3 transcripts by sponging let-7 microRNAs.

Conclusions:

  • Radiation resistance promotes metastasis in TNBC through increased ITGB3 expression.
  • Alterations in RNA metabolism, involving HNRNPL and circular RNAs, are key drivers of this radiation-induced metastatic phenotype.
  • Findings offer potential therapeutic targets for preventing metastasis in radiation-resistant cancers.

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