Decoding the Collagenome in Breast Cancer: Mechanotransduction, Microenvironment, and Translational Opportunities

Area of Science:

• Oncology
• Biochemistry
• Extracellular Matrix Biology

Background:

• The extracellular matrix (ECM) plays a critical role in breast cancer (BC) progression, affecting tumor growth, invasion, metastasis, immune response, and treatment outcomes.
• Collagens, key ECM components, act as structural proteins and mediate mechanotransduction, stromal interactions, and tumor cell behavior.

Purpose of the Study:

• To review collagen families and associated proteins in BC, detailing their expression, functions, clinical relevance, and therapeutic potential.
• To explore how collagen alterations influence the tumor microenvironment (TME) and impact BC progression and treatment resistance.

Main Methods:

• Narrative review of scientific literature.
• Analysis of collagen types (fibrillar, non-fibrillar, FACITs, MACITs, BM collagens, multiplexins) and their interactions.
• Integration of evidence on expression patterns, biological functions, and clinical significance.

Main Results:

• Altered collagen composition, organization, crosslinking, and degradation impact ECM stiffness, epithelial-mesenchymal transition (EMT), invasion, metastasis, and therapy resistance.
• Specific collagen types and fragments show potential as prognostic biomarkers and therapeutic targets, especially for HER2-positive and TNBC.
• The collagenome is a dynamic factor in the breast TME, influencing BC progression.

Conclusions:

• Collagen's multifaceted role in the breast TME highlights its importance in BC pathogenesis.
• Collagen-informed strategies are promising for improved patient stratification and targeted therapies in breast cancer.
• Further research into the collagenome could lead to novel therapeutic approaches for aggressive breast cancer.