Identification of TENM4 as a Novel Cancer Stem Cell-Associated Molecule and Potential Target in Triple Negative Breast Cancer

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Triple-negative breast cancer (TNBC) lacks targeted therapies, necessitating novel treatment strategies.
• Cancer stem cells (CSCs) are implicated in TNBC's rapid relapse and metastasis.
• Identifying CSC-associated targets is crucial for TNBC therapeutic development.

Purpose of the Study:

• To identify and characterize novel therapeutic targets for triple-negative breast cancer.
• To investigate the role of Teneurin 4 (TENM4) in TNBC, particularly in relation to cancer stem cells.

Main Methods:

• Comparative gene expression profiling of TNBC cancer stem cell-enriched tumorspheres and parental cells.
• Meta-analysis of breast cancer datasets to assess TENM4 mRNA levels and patient survival.
• Functional assays including TENM4 silencing to evaluate effects on tumorsphere formation, migration, and Focal Adhesion Kinase (FAK) phosphorylation.
• Analysis of TENM4 levels in plasma from tumor-bearing mice and TNBC patients.

Main Results:

• Teneurin 4 (TENM4) was identified as a significantly upregulated gene in TNBC CSCs.
• High TENM4 mRNA expression in invasive breast carcinoma correlates with shorter relapse-free survival in TNBC patients.
• TENM4 silencing reduced tumorsphere formation, migration, and FAK phosphorylation in mammary cancer cells.
• Elevated TENM4 levels were detected in plasma from tumor-bearing mice and TNBC patients.

Conclusions:

• TENM4 is upregulated in TNBC and associated with poor prognosis.
• TENM4 plays a role in key cancer stem cell functionalities, including tumorsphere formation and migration.
• TENM4 represents a promising novel biomarker and therapeutic target for triple-negative breast cancer.