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PLAC8 promotes adriamycin resistance via blocking autophagy in breast cancer

Yongxia Chen1, Yunlu Jia2, Misha Mao1

  • 1Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Journal of Cellular and Molecular Medicine
|June 12, 2021
PubMed

Insights

Higher PLAC8 protein expression in breast cancer correlates with Adriamycin (ADM) resistance. PLAC8 inhibits autophagy via p62, suggesting a new therapeutic target to overcome ADM resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Adriamycin (ADM) is a key chemotherapy for breast cancer, but resistance limits efficacy.
  • PLAC8, a conserved protein, acts as an oncogene or tumor suppressor in various cancers.
  • Increased PLAC8 expression is linked to poor outcomes and aggressive breast cancer phenotypes.

Purpose of the Study:

  • To investigate the role of PLAC8 in Adriamycin (ADM) resistance in breast cancer.
  • To elucidate the mechanism by which PLAC8 influences ADM sensitivity.
  • To explore the PLAC8/p62 pathway as a potential therapeutic target for overcoming ADM resistance.

Main Methods:

  • Correlative analysis of PLAC8 expression with clinical outcomes and tumor aggressiveness.
  • In vitro studies using siRNA and plasmid transfection to manipulate PLAC8 levels in breast cancer cells (MCF-7/ADMR).
  • Assessment of autophagy markers (LC3, p62) and drug sensitivity following modulation of PLAC8, autophagy activators (Rapamycin), and inhibitors (3-MA).

Main Results:

  • Higher PLAC8 expression correlated with worse prognosis and increased ADM resistance in breast cancer patients.
  • Overexpression of PLAC8 enhanced ADM resistance, while its inhibition sensitized cells to ADM.
  • PLAC8 blocked autophagy by inhibiting LC3 accumulation and increasing p62 levels, contributing to ADM resistance.
  • The PLAC8/p62 pathway synergized with autophagy inhibition to promote ADM resistance.

Conclusions:

  • PLAC8 promotes Adriamycin resistance in breast cancer by inhibiting the autophagy process, involving the p62 protein.
  • The PLAC8/p62 pathway represents a novel therapeutic target for overcoming ADM resistance in breast cancer patients.
  • Targeting this pathway may offer clinical applications for improving treatment outcomes in breast cancer.
Keywords:
PLAC8adriamycin resistanceautophagybreast cancerp62

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