Claudin 7 suppresses invasion and metastasis through repression of a smooth muscle actin program

Area of Science:

• Oncology
• Cell Biology
• Molecular Biology

Background:

• Metastasis, the spread of cancer cells, involves alterations in intercellular junctions.
• Claudins (CLDNs) are tight junction proteins with reduced expression in aggressive breast tumors.
• The specific role of Claudin 7 (CLDN7) in breast cancer metastasis is not well understood.

Purpose of the Study:

• To investigate the function of CLDN7 in breast cancer invasion and metastasis.
• To elucidate the molecular mechanisms by which CLDN7 influences cancer cell behavior.

Main Methods:

• Utilized gain- and loss-of-function genetics in murine breast cancer organoids.
• Performed transcriptomic analysis to identify gene expression changes.
• Validated findings in human breast cancer cell lines, tumor tissues, and public genomic datasets (bulk and single-cell RNA-seq).

Main Results:

• CLDN7 expression was found to suppress invasion and metastasis.
• Knockdown of CLDN7 induced smooth muscle actin (SMA)-related genes and a mesenchymal phenotype.
• An inverse correlation between CLDN7 and SMA-related gene expression was consistently observed across models.
• SMA-related genes were confirmed to promote breast cancer invasion.

Conclusions:

• CLDN7 acts as a suppressor of breast cancer invasion and metastasis.
• CLDN7 exerts its function by negatively regulating SMA-related and mesenchymal gene expression.
• These findings reveal a novel mechanism controlling breast cancer cell dissemination.