Mapping metastatic potential through cytoskeletal remodeling: A mechanobiology-based multi-cancer analysis.

Area of Science:

• Mechanobiology
• Cancer Biology
• Genomics

Background:

• Metastasis is the primary cause of cancer mortality, and current detection tools lack sensitivity for early metastatic potential.
• Existing gene expression assays often neglect crucial cellular dynamics like cytoskeletal remodeling and mechanotransduction.

Purpose of the Study:

• To identify and validate a novel gene panel associated with metastatic potential by analyzing mechanobiology-related genes.
• To evaluate the predictive value of these genes using multi-modal data across various cancer cell lines.

Main Methods:

• Curated a panel of 11 mechanobiology genes involved in actin cytoskeleton regulation.
• Utilized multi-modal data (gene expression, copy number variation, CRISPR, RNAi screens) from the DepMap database.
• Analyzed 351 cell lines from breast, pancreatic, and CNS tumors, stratified by tumor type and metastatic potential.

Main Results:

• Gene expression and copy number variation were the most informative parameters for predicting metastatic potential.
• FSCN1 showed consistent strong associations across tissues and correlated with canonical metastasis markers.
• A multi-gene signature including FSCN1, MYH9, ECM1, ANXA2, and EZR demonstrated robust performance and correlated with invasion, EMT, and stemness markers.

Conclusions:

• Introduced a novel, mechanobiologically driven gene panel (FSCN1, MYH9, ECM1, ANXA2, EZR) as a cross-cutting biomarker signature for metastatic potential.
• This panel captures mechanical and structural determinants of cell invasiveness, offering an advantage over conventional tumor-specific markers.
• The robustness and translational relevance of this gene panel are supported by its performance across diverse assays and alignment with core metastatic pathways.