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Cancer Stem Cells and Tumor Maintenance02:40

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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.
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The stem cell niche is the dynamic microenvironment where stem cells reside. Inside these niches, the cells may remain undifferentiated, undergo high self-renewal, or become lineage-specific progenitors. Stem cells coexist with other niche cells, such as stromal cells. They also interact closely with the ECM. Cell-cell and cell-matrix communication occur via adhesion molecules or soluble factors that signal the stem cells and determine their fate. Stromal cells also provide survival signals to...
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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.
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Updated: Jun 27, 2025

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Targeting Tumor Heterogeneity by Breaking a Stem Cell and Epithelial Niche Interaction Loop.

Rongze Ma1,2,3, Deyi Feng1,2, Jing Chen4

  • 1MOE Key Lab of Rare Pediatric Diseases & Hunan Key Laboratory of Medical Genetics of the School of Life Sciences, Hengyang, Hunan, 421001, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|May 6, 2024
PubMed
Summary

Tumor heterogeneity challenges cancer therapies. A newly identified FGF-BMP7-INHBA signaling loop in breast cancer stem cells and their niche can be targeted to inhibit tumor progression and overcome drug resistance.

Keywords:
BMP signalingFGF signalingdrug resistanceindividualized medicineintra‐tumoral heterogeneitymicroenvironmentprecision medicinetargeted therapy

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Area of Science:

  • Cell Biology
  • Cancer Research
  • Developmental Biology

Background:

  • Tumor heterogeneity presents a significant obstacle for effective cancer treatments.
  • Interactions between cancer cell subpopulations and their stromal niche, influencing cancer stem cell behavior, are poorly understood.

Purpose of the Study:

  • To elucidate the signaling pathways governing interactions between different cell populations in the mammary gland niche.
  • To investigate the role of these interactions in both organ regeneration and breast cancer progression.

Main Methods:

  • Investigated a positive feedback loop involving Fibroblast Growth Factor (FGF), Bone Morphogenetic Protein 7 (BMP7), and Inhibin Subunit Beta A (INHBA).
  • Examined the reciprocal dependence between basal stem cells and luminal epithelium, regulated by stromal-epithelial FGF signaling.

Main Results:

  • Identified an FGF-BMP7-INHBA signaling loop integrating mammary gland stem cells, luminal epithelial cells, and stromal fibroblasts.
  • Demonstrated that targeting this loop inhibits both organ regeneration and breast cancer progression.
  • Showcased the reciprocal dependence of basal stem cells and luminal epithelium mediated by BMP7 and INHBA, respectively.

Conclusions:

  • The identified signaling loop is crucial for mammary gland development and cancer progression.
  • Targeting this loop offers a potential strategy to overcome drug resistance driven by tumor heterogeneity.
  • Findings have significant implications for developing novel targeted therapies for breast cancer.