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An mRNA processing pathway suppresses metastasis by governing translational control from the nucleus

Albertas Navickas1,2,3,4,5, Hosseinali Asgharian1,2,3,4, Juliane Winkler6

  • 1Department of Biochemistry and Biophysics, University of California, San Francisco, CA, USA.

Nature Cell Biology
|May 8, 2023
PubMed

Insights

Heterogeneous nuclear ribonucleoprotein C (HNRNPC) controls cancer cell metastasis by regulating gene translation. Downregulation of HNRNPC in metastatic cells leads to poorer breast cancer prognosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Cancer cells utilize post-transcriptional regulation for metastasis.
  • Translational control's role in cancer progression is not fully understood.

Purpose of the Study:

  • To investigate translational control mechanisms in breast cancer metastasis.
  • To identify key regulators of metastatic gene expression.

Main Methods:

  • Ribosome profiling to compare translation efficiencies in cells with varying metastatic potential.
  • Development of regression-based methods for analyzing ribosome profiling and alternative polyadenylation data.
  • Xenograft mouse models to assess the impact of HNRNPC modulation on metastasis.

Main Results:

  • Identified heterogeneous nuclear ribonucleoprotein C (HNRNPC) as a translational controller.
  • HNRNPC downregulation in highly metastatic cells leads to 3' UTR lengthening and translational repression of target mRNAs.
  • Modulating HNRNPC expression affects breast cancer cell metastatic capacity in vivo.
  • Reduced HNRNPC expression correlates with worse prognosis in breast cancer patients.

Conclusions:

  • HNRNPC is a critical regulator of mRNA translation impacting breast cancer metastasis.
  • The HNRNPC-mediated translational control pathway is a potential therapeutic target.
  • HNRNPC downregulation serves as a biomarker for poor prognosis in breast cancer.

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