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Flow Cytometric Detection of Newly-formed Breast Cancer Stem Cell-like Cells After Apoptosis Reversal
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Flow Cytometric Detection of Newly-formed Breast Cancer Stem Cell-like Cells After Apoptosis Reversal

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Cytokeratin 8/18 protects breast cancer cell lines from TRAIL-induced apoptosis

William P Bozza1, Yaqin Zhang1, Baolin Zhang1

  • 1Office of Biotechnology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA.

Oncotarget
|May 26, 2018
PubMed

Insights

Keratin 8/18 proteins reduce cancer cell death signaling via TRAIL. Lowering these keratins may improve effectiveness of TRAIL-based cancer therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Death Pathways

Background:

  • Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers apoptosis through death receptors (DRs) 4 and/or 5.
  • Clinical applications of TRAIL-based cancer therapies show limited efficacy due to undefined resistance mechanisms.

Purpose of the Study:

  • To investigate the role of intermediate filament proteins, keratin 8 and keratin 18 (K8/K18), in regulating TRAIL-induced apoptosis.
  • To explore K8/K18 as a potential mechanism of resistance to TRAIL-targeted cancer therapies.

Main Methods:

  • Comparative analysis of K8/K18 protein levels in TRAIL-sensitive versus TRAIL-resistant breast cancer cell lines.
  • Investigating the effects of K8 blockade and K8/K18 ectopic expression on DR5 levels and TRAIL sensitivity.

Main Results:

  • Higher K8/K18 protein levels correlate with TRAIL resistance in breast cancer cells.
  • K8 blockade enhances surface DR5 expression and TRAIL-induced apoptosis.
  • Ectopic expression of K8/K18 downregulates DR5 protein levels.

Conclusions:

  • Keratin 8/18 negatively regulates TRAIL-induced apoptosis signaling through DR5 in breast cancer.
  • K8/K18 may serve as a predictive biomarker for resistance to DR5-targeted cancer therapies.
Keywords:
apoptosisbreast cancerdeath receptordrug resistancekeratin 8

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