WNT signaling and cancer stemness

Area of Science:

• Oncology
• Molecular Biology
• Cancer Stem Cell Biology

Background:

• Cancer stemness, characterized by self-renewal and tumor initiation, is regulated by specific signaling networks.
• WNT signaling pathways, both canonical and noncanonical, play crucial roles in cancer stem cell (CSC) functions, including proliferation, dormancy, and epithelial-mesenchymal transition (EMT).
• The tumor microenvironment, influenced by WNT signaling, involves interactions with fibroblasts, endothelial cells, and immune cells, impacting cancer progression and immune evasion.

Purpose of the Study:

• To elucidate the multifaceted roles of WNT signaling in regulating cancer stemness.
• To discuss how WNT signaling orchestrates cancer cell plasticity, including proliferation/dormancy, EMT, and immune landscape modulation.
• To review investigational drugs targeting WNT signaling cascades for therapeutic intervention.

Main Methods:

• Review of canonical and noncanonical WNT signaling pathways and their downstream targets.
• Analysis of WNT signaling crosstalk with other pathways like TGFβ.
• Discussion of WNT-related cancer stemness features and their clinical implications.

Main Results:

• Canonical WNT signaling promotes CSC expansion and influences immune responses.
• Noncanonical WNT signaling maintains quiescent CSCs and drives EMT, often collaborating with TGFβ signaling for immune evasion.
• WNT signaling networks orchestrate the tumor microenvironment and fine-tune stemness across various cancers.

Conclusions:

• WNT signaling is a central regulator of cancer stemness and plasticity, impacting proliferation, EMT, and immune evasion.
• Investigational therapies targeting WNT signaling pathways show promise for cancer treatment.
• Further research into context-dependent reprogramming is needed to optimize WNT-targeted therapies for improved clinical outcomes.