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Identification of protein kinase inhibitors to reprogram breast cancer cells

Jie Yuan1,2,3, Fan Zhang1, Meng You1

  • 1Cancer Biology Division, Department of Radiation Oncology, Washington University School of Medicine, Saint Louis, MO, 63108, USA.

Cell Death & Disease
|September 13, 2018
PubMed

Insights

New research shows kinase inhibitors can reprogram breast cancer cells into normal fat cells, offering a potential new treatment. This method avoids transcription factors and shows promise for preventing cancer recurrence.

Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • Direct reversion of cancer to normal tissue is an ideal cancer treatment strategy.
  • Transcription factors have shown potential in reprogramming cancer cells into pluripotent stem cells.

Purpose of the Study:

  • To develop a novel reprogramming method for breast cancer treatment using kinase inhibitors.
  • To investigate if Rho-associated protein kinase (ROCK) and mammalian target of rapamycin (mTOR) inhibitors can reprogram breast cancer cells.

Main Methods:

  • Screening a kinase inhibitor library to identify effective compounds.
  • Utilizing ROCK and mTOR inhibitors to reprogram breast cancer cells.
  • Genome-wide transcriptional analysis to compare cell profiles.
  • In vitro and in vivo tumorigenesis assays to assess cell behavior.

Main Results:

  • ROCK and mTOR inhibitors successfully reprogrammed breast cancer cells into progenitor and adipogenic cells.
  • Induced fat-like cells exhibited transcriptional profiles similar to normal adipocytes.
  • These reprogrammed cells demonstrated reduced proliferation and tumorigenicity.
  • Reprogramming treatment prevented local recurrence of breast cancer in mice.

Conclusions:

  • ROCK-mTOR inhibitors offer a transcription factor-free method for reprogramming breast cancer cells.
  • This approach converts malignant cells into non-tumorigenic adipocytes.
  • The strategy holds significant potential for clinical translation in breast cancer therapy due to existing drug availability.

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