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Targeting ASCT2-mediated glutamine uptake blocks prostate cancer growth and tumour development

Qian Wang1,2,3, Rae-Anne Hardie1,2,3, Andrew J Hoy4

  • 1Origins of Cancer Laboratory, Centenary Institute, Camperdown, NSW, Australia.

The Journal of Pathology
|February 20, 2015
PubMed

Insights

The glutamine transporter ASCT2 is crucial for prostate cancer growth and metastasis. Inhibiting ASCT2 blocks cancer cell proliferation by affecting nutrient uptake and cell cycle progression, marking it as a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Metabolism

Background:

  • Glutamine is vital for cancer cells, serving as a source for macromolecules and fueling the tricarboxylic acid (TCA) cycle.
  • Prostate cancer cells exhibit high expression of the glutamine transporter ASCT2 (SLC1A5).

Purpose of the Study:

  • To investigate the role of ASCT2-mediated glutamine uptake in prostate cancer progression.
  • To evaluate ASCT2 as a potential therapeutic target for prostate cancer.

Main Methods:

  • Utilized LNCaP and PC-3 prostate cancer cell lines for in vitro studies.
  • Employed chemical inhibition and shRNA-mediated knockdown of ASCT2.
  • Assessed glutamine uptake, cell cycle progression, mTORC1 pathway activation, and metabolic functions.
  • Evaluated tumor growth and metastasis in PC-3 cell xenografts in vivo.

Main Results:

  • Inhibition of ASCT2 reduced glutamine uptake, cell cycle progression (E2F factors), mTORC1 activation, and cell growth in vitro.
  • Chemical inhibition of ASCT2 decreased oxygen consumption and fatty acid synthesis.
  • ASCT2 knockdown in xenografts significantly inhibited tumor growth and metastasis, with decreased E2F pathway proteins.

Conclusions:

  • ASCT2-mediated glutamine uptake is essential for prostate cancer cell cycle regulation and growth.
  • ASCT2 plays a critical role in supporting downstream metabolic pathways vital for cancer progression.
  • Targeting ASCT2 presents a promising therapeutic strategy for prostate cancer treatment.
Keywords:
ASCT2SLC1A5cell cycleglutaminemetabolismprostate cancer

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