The JNK and Hippo pathways control epithelial integrity and prevent tumor initiation by regulating an overlapping...

Area of Science:

• Cell Biology
• Developmental Biology
• Cancer Biology

Background:

• Epithelial organs possess mechanisms to eliminate compromised cells, preventing tumor formation.
• Apicobasal polarity loss in cells can lead to neoplastic transformation.
• Signaling pathways like Jun-N-terminal kinase (JNK) and Hippo play critical roles in cellular homeostasis.

Purpose of the Study:

• To elucidate the molecular mechanisms by which JNK and Hippo pathways regulate epithelial integrity.
• To identify the transcription factors and target genes involved in preventing tumor initiation.
• To understand how defective cells are recognized and removed to maintain organ homeostasis.

Main Methods:

• Targeted DamID experiments in Drosophila melanogaster eye imaginal discs.
• Analysis of transcription factor binding and gene expression.
• Investigating the interplay between AP-1, Hippo pathway components (Yorkie, Scalloped), and CtBP.

Main Results:

• Jun (AP-1) and Hippo pathway regulators (Yorkie, Scalloped) bind to overlapping gene sets promoting organ growth.
• In neoplastic cells, AP-1 transcription factors, with CtBP, repress growth-promoting genes.
• Failure of AP-1/CtBP-mediated repression allows Yorkie/Scalloped to drive tumor growth.

Conclusions:

• AP-1/CtBP acts in parallel to Yorkie/Scalloped to repress a shared set of growth genes.
• This coordinated repression is crucial for eliminating defective cells and preventing tumor initiation.
• The findings reveal a novel mechanism for maintaining epithelial integrity and tumor suppression.