Tumors exploit interclonal Hedgehog-Wnt crosstalk to drive tumor-promoting cell competition.
Malignant tumor clones hijack interclonal Hedgehog-Wnt signaling to convert cell competition into a driver of tumor growth, as shown in Drosophila and human pancreatic cancer.
- Why it matters: Understanding how tumor heterogeneity promotes progression and therapy resistance is crucial, yet the mechanisms of cooperation between different cancer cell subclones remain unclear.
- What they did: The study used genetic and molecular approaches in Drosophila and human models, revealing that RAS-mutant "loser" cells activate Hedgehog signaling and secrete Wingless, which reprograms neighboring clones into invasive super-competitors.
- The result: This interclonal Hedgehog-Wnt crosstalk accelerates tumor growth and clonal selection, highlighting a conserved pathway that could be targeted to disrupt tumor ecosystem dynamics and improve therapies.