Internal medicine

Cytoskeleton

Pathology

Cell

Contractility

Cell polarity

Biology

Cancer

Endocrinology

Cell migration

Focal adhesion

Extracellular matrix

Stromal cell

Chemistry

Metastasis

Stress fiber

Cell biology

Biochemistry

Medicine

Proceedings of the National Academy of Sciences

Significance Tumor progression to enable metastasis includes remodeling the wavy bundles of collagen making up the tissue stromal extracellular matrix (ECM) into straight bundles within the tumor microenvironment. While wavy collagen bundles are thought to be inhibitory to cell polarization and migration in tissue, straight ECM fibers are thought to be conducive, thereby mediating metastasis. We used nanofabricated cell culture substrates that mimic the ECM fiber waveforms seen in both benign- and metastases-promoting tumor ECMs. Large amplitude ECM waves depolarized tumor cells and decreased directional migration via cell contractility-mediated organization of the cytoskeleton and adhesions. Thus, ECM architecture of normal tissue and benign tumors may generally inhibit tumor cell exit, but this may be overcome by increasing tumor cell contractility.

Contractility, focal adhesion orientation, and stress fiber orientation drive cancer cell polarity and migration along wavy ECM substrates