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LRP8 is overexpressed in estrogen-negative breast cancers and a potential target for these tumors

Virginie Maire1,2, Faisal Mahmood1,2, Guillem Rigaill3,4

  • 1Translational Research Department, Institut Curie, PSL Research University, Paris, France.

Cancer Medicine
|December 22, 2018
PubMed

Insights

Targeting low-density lipoprotein receptor-related protein 8 (LRP8) shows promise for treating triple-negative breast cancer (TNBC). LRP8 depletion inhibits proliferation and induces cell death, offering new therapeutic avenues for aggressive breast cancer subtypes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Triple-negative breast cancer (TNBC) presents the poorest prognosis among breast cancer subtypes, necessitating novel therapeutic strategies.
  • Estrogen receptor-negative breast tumors, including TNBC and HER2-overexpressing types, exhibit distinct molecular profiles compared to luminal subtypes and normal tissues.

Purpose of the Study:

  • To identify novel therapeutic targets for triple-negative breast cancer (TNBC) through transcriptome microarray analysis.
  • To investigate the role of low-density lipoprotein receptor-related protein 8 (LRP8) as a potential therapeutic target in TNBC.

Main Methods:

  • Transcriptome microarray analysis was employed to compare gene expression profiles in different breast cancer subtypes and normal tissues.
  • Functional studies involved LRP8 depletion in TNBC and HER2-overexpressing cell lines to assess effects on proliferation, cell cycle, and apoptosis.
  • In vivo efficacy was evaluated using a xenograft model to assess the impact of LRP8 depletion on tumor growth.

Main Results:

  • Low-density lipoprotein receptor-related protein 8 (LRP8) expression was significantly higher in estrogen receptor-negative breast tumors (TNBC, HER2+) compared to luminal tumors and normal breast tissue.
  • LRP8 depletion markedly reduced cell proliferation in TNBC and HER2-overexpressing cell lines, inducing G1 cell cycle arrest and programmed cell death.
  • LRP8 is essential for anchorage-independent growth in vitro and its inhibition slowed tumor growth in vivo.

Conclusions:

  • LRP8 is a promising therapeutic target for hormone-negative breast cancers, including TNBC and HER2-overexpressing subtypes.
  • Targeting LRP8 may offer a novel treatment strategy to improve outcomes for patients with aggressive breast cancer.
  • Further investigation into LRP8-targeting therapies is warranted for clinical development in specific breast cancer populations.
Keywords:
HER2LRP8apoptosistargeted therapytriple-negative breast cancer

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