Wingless modulates activator protein-1-mediated tumor invasion

Area of Science:

• Oncology
• Molecular Biology
• Cell Biology

Background:

• Metastasis is a leading cause of cancer mortality, yet the role of the Wnt/β-catenin pathway in tumor invasion is debated.
• Understanding the mechanisms of tumor metastasis is crucial for developing effective cancer treatments.

Purpose of the Study:

• To investigate the role of the Wingless (Wg) pathway in regulating tumor invasion using Drosophila models.
• To elucidate the molecular mechanisms connecting cell polarity, JNK signaling, and Wnt pathway activation in tumor progression.

Main Methods:

• Utilized established Drosophila tumor models to study Wg pathway function in tumor invasion.
• Investigated the role of JNK signaling and the transcription factor AP-1 in regulating Wg expression.
• Confirmed the conservation of AP-1 mediated WNT transcriptional activation in human cancer cells.

Main Results:

• Wg signaling is essential for cell polarity disruption-induced cell migration and epithelial-mesenchymal transition (EMT)-like changes.
• Reduced Wg signaling inhibited tumor invasion in Drosophila models.
• JNK signaling activation by cell polarity disruption upregulates Wg expression via AP-1 binding to a conserved site in the wg gene.
• Cooperation between Arm and RasV12 was sufficient to induce tumor invasion.

Conclusions:

• The Wnt/β-catenin pathway plays a pro-invasive role in cancer metastasis.
• A conserved mechanism links JNK signaling and Wnt pathway activation through AP-1, promoting tumor invasion.
• This pathway provides a potential target for anti-metastasis therapies.