1. Cell contractility drives mechanical memory of oral squamous cell carcinoma
- Author
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Moon, So Youn, de Campos, Paloma Santos, Matte, Bibiana Franzen, Placone, Jesse K, Zanella, Virgı lio G, Martins, Manoela D, Lamers, Marcelo Lazzaron, and Engler, Adam J
- Subjects
Biochemistry and Cell Biology ,Biological Sciences ,Cancer ,Rare Diseases ,Dental/Oral and Craniofacial Disease ,2.1 Biological and endogenous factors ,Aetiology ,Humans ,Carcinoma ,Squamous Cell ,Mouth Neoplasms ,Squamous Cell Carcinoma of Head and Neck ,Proto-Oncogene Proteins c-akt ,Cell Movement ,Epithelial-Mesenchymal Transition ,Head and Neck Neoplasms ,Cell Line ,Tumor ,Medical and Health Sciences ,Developmental Biology ,Biochemistry and cell biology - Abstract
Matrix stiffening is ubiquitous in solid tumors and can direct epithelial-mesenchymal transition (EMT) and cancer cell migration. Stiffened niche can even cause poorly invasive oral squamous cell carcinoma (OSCC) cell lines to acquire a less adherent, more migratory phenotype, but mechanisms and durability of this acquired "mechanical memory" are unclear. Here, we observed that contractility and its downstream signals could underlie memory acquisition; invasive SSC25 cells overexpress myosin II (vs. noninvasive Cal27 cells) consistent with OSCC. However, prolonged exposure of Cal27 cells to a stiff niche or contractile agonists up-regulated myosin and EMT markers and enabled them to migrate as fast as SCC25 cells, which persisted even when the niche softened and indicated "memory" of their prior niche. Stiffness-mediated mesenchymal phenotype acquisition required AKT signaling and was also observed in patient samples, whereas phenotype recall on soft substrates required focal adhesion kinase (FAK) activity. Phenotype durability was further observed in transcriptomic differences between preconditioned Cal27 cells cultured without or with FAK or AKT antagonists, and such transcriptional differences corresponded to discrepant patient outcomes. These data suggest that mechanical memory, mediated by contractility via distinct kinase signaling, may be necessary for OSCC to disseminate.
- Published
- 2023