LATS2 suppresses oncogenic Wnt signaling by disrupting β-catenin/BCL9 interaction

Area of Science:

• Molecular Biology
• Oncology
• Biochemistry

Background:

• Aberrant Wnt/β-catenin signaling drives various human cancers.
• Understanding the regulation of this pathway is crucial for cancer therapy.

Purpose of the Study:

• To investigate the role of LATS2 in regulating Wnt/β-catenin-mediated transcription.
• To explore LATS2 as a potential therapeutic target in cancer.

Main Methods:

• Investigated the interaction between LATS2 and β-catenin using co-immunoprecipitation.
• Assessed LATS2 binding to Wnt target gene promoters via ChIP-qPCR.
• Evaluated the effect of LATS2 on the β-catenin/BCL9 interaction.
• Correlated LATS2 expression with Wnt target gene levels in colorectal cancer tissues.
• Assessed the in vivo effect of nocodazole-induced LATS2 on tumor growth.

Main Results:

• LATS2 directly interacts with β-catenin and localizes to Wnt target gene promoters.
• LATS2 inhibits the β-catenin/BCL9 interaction, independent of its kinase activity.
• LATS2 expression is downregulated in colorectal cancers and inversely correlates with Wnt target gene expression.
• Nocodazole treatment increases LATS2 levels, suppressing tumor growth in vivo by targeting the β-catenin/BCL9 complex.

Conclusions:

• LATS2 acts as a tumor suppressor by inhibiting oncogenic Wnt/β-catenin signaling.
• LATS2's mechanism involves disrupting the β-catenin/BCL9 interaction.
• LATS2 downregulation in cancer suggests its potential as a therapeutic target for anticancer strategies.