Related Experiment Video

Updated: Nov 5, 2025

Murine Prostate Micro-dissection and Surgical Castration
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Murine Prostate Micro-dissection and Surgical Castration

Published on: May 11, 2016

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SLFN5 Regulates LAT1-Mediated mTOR Activation in Castration-Resistant Prostate Cancer

Rafael S Martinez1,2, Mark J Salji1,2, Linda Rushworth1,2

  • 1CRUK Beatson Institute, Garscube Estate, Glasgow, United Kingdom.

Cancer Research
|May 14, 2021
PubMed

Insights

Schlafen family member 5 (SLFN5) is a novel target in castration-resistant prostate cancer (CRPC). SLFN5 regulates amino acid transport and mTORC1 signaling, impacting CRPC tumor growth.

Area of Science:

  • Oncology
  • Molecular Biology
  • Metabolism

Background:

  • Androgen deprivation therapy (ADT) is standard for prostate cancer, but resistance leads to lethal castration-resistant prostate cancer (CRPC).
  • Heterogeneity in CRPC models complicates treatment strategies.
  • Understanding molecular mechanisms driving CRPC is crucial for developing new therapies.

Purpose of the Study:

  • To identify novel molecular targets in CRPC.
  • To investigate the role of Schlafen family member 5 (SLFN5) in CRPC progression.
  • To elucidate the mechanism by which SLFN5 influences CRPC growth.

Main Methods:

  • Comparative proteomic analysis of matched hormone-naïve and CRPC orthograft models.
  • In vivo studies involving SLFN5 depletion in CRPC models.
  • Investigation of SLFN5 interaction with ATF4 and regulation of LAT1.
  • Analysis of amino acid transport and mTORC1 signaling pathways.

Main Results:

  • SLFN5 is upregulated in CRPC and associated with poor patient outcomes.
  • SLFN5 depletion significantly inhibits CRPC tumor growth under castrated conditions.
  • SLFN5 interacts with ATF4, upregulating the amino acid transporter LAT1.
  • SLFN5 depletion reduces intracellular essential amino acids and impairs mTORC1 signaling via LAT1.

Conclusions:

  • SLFN5 is a key regulator of amino acid metabolism and mTORC1 signaling in CRPC.
  • SLFN5 represents a promising therapeutic target for overcoming castration resistance in prostate cancer.
  • The identified orthograft models effectively recapitulate CRPC heterogeneity.

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