Signaling pathway inhibitors target breast cancer stem cells in triple-negative breast cancer

Wenlong Li1, Hongmei Yang1, Xiaoli Li2

  • 1Department of Breast Surgery, The First Bethune Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.

Oncology Reports
|October 27, 2018
PubMed

Insights

Five signaling pathway inhibitors show promise in targeting breast cancer stem cells (BCSCs) for triple-negative breast cancer (TNBC) treatment. These agents reduced tumor growth and spread in preclinical models, offering new therapeutic strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Stem Cell Research

Background:

  • Triple-negative breast cancer (TNBC) is an aggressive subtype with limited therapeutic options.
  • Breast cancer stem cells (BCSCs) are implicated in tumor recurrence and metastasis.
  • Targeting BCSCs offers a promising strategy for effective TNBC treatment.

Purpose of the Study:

  • To evaluate the efficacy of five signaling pathway inhibitors as novel therapeutic agents against BCSCs in TNBC.
  • To investigate the in vitro and in vivo effects of these inhibitors on TNBC cell proliferation, invasion, apoptosis, and self-renewal.
  • To explore the potential of these inhibitors for clinical application in TNBC patients.

Main Methods:

  • In vitro studies utilized MTT assays, Matrigel invasion assays, flow cytometry, and mammosphere assays on the HCC38 TNBC stem cell line.
  • In vivo studies involved xenograft mouse models using the HCC1806 TNBC stem cell line.
  • Assessment of protein expression and phosphorylation of downstream signaling molecules was performed.

Main Results:

  • Signaling pathway inhibitors significantly reduced TNBC cell proliferation, invasion, and mammosphere formation in vitro.
  • These agents induced apoptosis in TNBC cells by inhibiting key signaling molecules.
  • In vivo studies demonstrated effective suppression of tumor formation and growth in xenograft models.

Conclusions:

  • The investigated signaling pathway inhibitors demonstrate significant potential as novel therapeutic agents targeting BCSCs in TNBC.
  • These findings suggest a promising therapeutic strategy for TNBC by targeting BCSCs.
  • The study provides valuable insights for potential clinical applications in TNBC treatment.

Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
8.9K
Cancer Stem Cells and Tumor Maintenance02:40

Cancer Stem Cells and Tumor Maintenance

Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
6.0K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.8K
Distinctive Features of Adult Stem Cells vs Cancer Stem Cells01:18

Distinctive Features of Adult Stem Cells vs Cancer Stem Cells

A stem cell is an unspecialized cell that can divide without limit as needed and can, under specific conditions, differentiate into specialized cells.
Adult stem cells
Adult stem cells are tissue-specific; hence, they divide to develop the tissue from which they originate. One type of adult stem cell is the epithelial stem cell, which gives rise to the keratinocytes in the multiple layers of epithelial cells in the epidermis of the skin. Adult bone marrow has three distinct types of stem cells:...
4.5K
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
6.6K