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Updated: May 25, 2025

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Notch and Hedgehog Signaling Unveiled: Crosstalk, Roles, and Breakthroughs in Cancer Stem Cell Research

Sabina Iluta1, Madalina Nistor2, Sanda Buruiana3

  • 1Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, 400124 Cluj Napoca, Romania.

Life (Basel, Switzerland)
|February 26, 2025
PubMed

Insights

Targeting cancer stem cells (CSCs) requires understanding complex signaling pathways like Notch and Hedgehog (Hh). This review explores their roles in cancer and the tumor microenvironment for better therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Cancer stem cells (CSCs) and bulk tumor cells are key therapeutic targets.
  • Notch and Hedgehog (Hh) signaling pathways are implicated in CSC stemness and metastasis.
  • Crosstalk between signaling pathways complicates targeted cancer therapy development.

Purpose of the Study:

  • To review the roles of Notch and Hh signaling in cancer.
  • To examine the intersection of Notch and Hh pathways with each other and other networks (Wnt/β-catenin, TGF, JAK/STAT3).
  • To explore the influence of the tumor microenvironment (TME) on CSC development and maintenance.

Main Methods:

  • Literature review and synthesis of existing research on cancer signaling pathways.
  • Analysis of the crosstalk between Notch, Hh, Wnt/β-catenin, TGF, and JAK/STAT3 pathways.
  • Investigation of the tumor microenvironment's role in CSC regulation.

Main Results:

  • Notch and Hh pathways are critical for CSC maintenance and contribute to metastasis.
  • Complex interactions exist between Notch, Hh, and other signaling networks (Wnt/β-catenin, TGF, JAK/STAT3).
  • The tumor microenvironment significantly influences CSC behavior and therapeutic resistance.

Conclusions:

  • Understanding the intricate crosstalk of signaling pathways is essential for developing effective CSC-targeting therapies.
  • Targeting CSCs and their microenvironment may overcome therapy resistance.
  • Further research into pathway intersections can guide the development of novel, long-term cancer treatments.
Keywords:
Hedgehog signalingNotch signaling pathwaycancer stem cellscancer therapytumor biologytumor microenvironment

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