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Low doses of Paclitaxel repress breast cancer invasion through DJ-1/KLF17 signalling pathway

Ismail Ahmed Ismail1,2, Gamal H El-Sokkary3, Saber H Saber2

  • 1Faculty of Science, Department of Biology, Taibah University, Saudi, Arabia.

Clinical and Experimental Pharmacology & Physiology
|April 28, 2018
PubMed

Insights

Low doses of paclitaxel (taxol) inhibit breast cancer metastasis by affecting cell invasion and migration. This study reveals paclitaxel regulates the DJ-1/KLF17/ID-1 signaling pathway, impacting tumor spread.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Paclitaxel (taxol) is a key chemotherapy agent used against various tumors, including breast cancer.
  • Conflicting evidence exists regarding paclitaxel's effect on breast cancer metastasis, and its underlying mechanisms remain unclear.
  • This study investigates the impact of low-dose paclitaxel on breast cancer metastasis and its regulatory mechanisms.

Purpose of the Study:

  • To determine the effect of low-dose paclitaxel on breast cancer cell invasion and migration.
  • To elucidate the molecular mechanisms by which paclitaxel influences breast cancer metastasis.
  • To identify key molecular targets and pathways regulated by paclitaxel in breast cancer.

Main Methods:

  • Utilized MCF-7 and MDA-MB-231 breast cancer cell lines.
  • Assessed cytotoxicity, cell invasion, and migration following paclitaxel treatment.
  • Quantified mRNA and protein expression levels of key genes including Snail, E-cadherin, DJ-1, ID-1, and KLF17.

Main Results:

  • Paclitaxel demonstrated significant cytotoxicity at low doses in both cell lines.
  • Low-dose paclitaxel inhibited cell invasion and migration.
  • Paclitaxel treatment led to decreased Snail and increased E-cadherin mRNA expression.
  • Down-regulation of DJ-1 and ID-1 mRNA, alongside increased KLF17 mRNA, was observed.
  • Paclitaxel induced KLF17 and repressed ID-1 protein levels.

Conclusions:

  • Paclitaxel, even at low doses, inhibits breast cancer metastasis by reducing cell invasion and migration.
  • The mechanism involves the regulation of the DJ-1/KLF17/ID-1 signaling pathway.
  • Specifically, paclitaxel represses DJ-1 and ID-1 expression while enhancing KLF17 expression, thereby inhibiting metastasis.
Keywords:
DJ-1KLF17breast cancer metastasispaclitaxel

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