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Targeting LRP8 inhibits breast cancer stem cells in triple-negative breast cancer

Chang-Ching Lin1, Miao-Chia Lo1, Rebecca Moody2

  • 1Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, MI, 48109, USA.

Cancer Letters
|September 19, 2018
PubMed

Insights

Triple-negative breast cancer (TNBC) is hard to treat. This study finds LRP8 promotes cancer stem cells in TNBC, suggesting LRP8 as a new therapeutic target to improve treatment outcomes.

Area of Science:

  • Oncology
  • Molecular Biology

Background:

  • Triple-negative breast cancer (TNBC) presents significant therapeutic challenges due to limited targeted treatments.
  • Breast cancer stem cells (BCSCs) are implicated in TNBC's chemoresistance and metastatic potential.

Purpose of the Study:

  • To identify novel regulators of BCSCs in TNBC.
  • To investigate the role of LRP8 in TNBC progression and therapeutic sensitivity.

Main Methods:

  • Expression analysis of LRP8 in breast cancer subtypes.
  • LRP8 knockdown in TNBC cell lines.
  • Assessment of Wnt/β-catenin signaling pathway activity.
  • Evaluation of BCSC populations and tumorigenic potential in xenograft models.
  • Analysis of cellular phenotype and chemosensitivity post-LRP8 knockdown.

Main Results:

  • LRP8 is highly expressed and its locus amplified in TNBC.
  • LRP8 knockdown inhibits Wnt/β-catenin signaling, reduces BCSCs, and suppresses tumor growth.
  • LRP8 inhibition promotes a differentiated phenotype and enhances chemotherapy sensitivity in TNBC cells.

Conclusions:

  • LRP8 acts as a positive regulator of BCSCs in TNBC.
  • Targeting LRP8 represents a promising therapeutic strategy for TNBC by suppressing BCSCs and overcoming chemoresistance.
Keywords:
Breast cancer stem cellsLRP8Triple-negative breast cancerTumorigenesisWnt/β-catenin signaling

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