S100A11 is involved in the progression of colorectal cancer through the desmosome-catenin-TCF signaling pathway

Area of Science:

• Molecular biology
• Cancer research
• Cell biology

Background:

• S100A11 protein is highly expressed in various cancers, including squamous cell carcinoma, mesothelioma, and pancreatic cancer.
• Previous research focused on the extracellular role of S100A11 in cancer progression.
• The intracellular functions of S100A11, particularly in colorectal cancer, remain largely unelucidated.

Purpose of the Study:

• To investigate the intracellular functions of S100A11 in cancer cells.
• To focus on colorectal cancer cells, where S100A11 is abundant but poorly studied.
• To identify novel intracellular binding partners and pathways regulated by S100A11.

Main Methods:

• Investigated the effect of S100A11 overexpression and downregulation on colorectal cancer cell proliferation and migration.
• Identified S100A11 binding proteins using molecular approaches.
• Analyzed the interaction of S100A11 with desmosome proteins and its effect on the TCF pathway.

Main Results:

• Overexpression of S100A11 significantly promoted proliferation and migration in colorectal cancer cells.
• Downregulation of S100A11 inversely inhibited these cancer behaviors.
• Identified novel intracellular binding partners for S100A11, including desmosome proteins like DSG1.
• Demonstrated that S100A11 regulates DSG1 expression and activates the TCF pathway via promoting nuclear translocation of γ-catenin.

Conclusions:

• Intracellular S100A11 plays a critical role in promoting colorectal cancer cell proliferation and migration.
• S100A11 interacts with desmosome components, specifically regulating DSG1 expression.
• A novel pathway involving S100A11, DSG1, γ-catenin, and the TCF pathway is identified, offering new insights into colorectal cancer.
• Understanding the intracellular functions of S100A11 provides a basis for developing targeted cancer therapies.