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Updated: Aug 5, 2025

Analysis of SCAP N-glycosylation and Trafficking in Human Cells
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MBTPS2 acts as a regulator of lipogenesis and cholesterol synthesis through SREBP signalling in prostate cancer

Amy J Tibbo1,2, Andrew Hartley1,2, Richa Vasan1,2

  • 1School of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G61 1QH, UK.

British Journal of Cancer
|March 29, 2023
PubMed
Abstract

Insights

MBTPS2 alteration is linked to metastatic prostate cancer. Its silencing impairs cancer cell growth and affects fatty acid and cholesterol metabolism, offering potential therapeutic targets for advanced disease.

Area of Science:

  • Oncology
  • Molecular Biology
  • Metabolism

Background:

  • Prostate cancer is a leading cause of cancer death in men, primarily due to advanced and metastatic disease.
  • Current treatments lack curative options for metastatic prostate cancer.
  • Identifying novel molecular drivers of metastasis is crucial for developing new therapies.

Purpose of the Study:

  • To investigate the role of MBTPS2 (Membrane Bound Transcription Factor Peptidase, Site 2) in prostate cancer progression and metastasis.
  • To elucidate the functional impact of MBTPS2 alterations on cellular metabolism, specifically fatty acid and cholesterol pathways.

Main Methods:

  • Utilized a Sleeping Beauty transposon system for unbiased in vivo genetic screening in a murine prostate cancer model.
  • Performed MBTPS2 knockdown using siRNA in human prostate cancer cell lines (LNCaP, DU145, PC3).
  • Conducted RNA-sequencing (RNA-Seq) and quantitative PCR (qPCR) to analyze gene expression changes and validated metabolic pathways. Employed Filipin III staining to assess cholesterol metabolism.

Main Results:

  • MBTPS2 was identified as a gene associated with metastatic prostate cancer through in vivo screening.
  • MBTPS2 knockdown significantly reduced proliferation and colony formation in human prostate cancer cells.
  • Silencing MBTPS2 impaired cholesterol synthesis and uptake, and reduced the expression of fatty acid synthesis regulators (FASN, ACACA) in LNCaP cells.

Conclusions:

  • MBTPS2 plays a significant role in the progression of prostate cancer.
  • MBTPS2's involvement in metastatic prostate cancer may be mechanistically linked to its regulation of fatty acid and cholesterol metabolism.
  • Targeting MBTPS2 could represent a novel therapeutic strategy for managing advanced prostate cancer.

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