Aug 9, 2019

A mechanical memory of pancreatic cancer cells

BioRxiv : the Preprint Server for Biology
Ilaria CarnevaleStefano Coppola

Abstract

Cells sense and respond to mechanical stimuli in healthy and pathological conditions. Although the major mechanisms underlying cellular mechanotransduction have been described, it remains largely unclear how cells store information on past mechanical cues over time. Such mechanical memory is extremely relevant in the onset of metastasis in which cancer cells migrate through tissues of different stiffness, e.g. from a stiffer tumor microenvironment to softer metastatic sites as commonly occurs for pancreatic cancer. Here, we used micropillar-based traction force microscopy to show that Suit-2.28 pancreatic cancer cells mechanically primed on a stiff matrix exerted higher traction forces even when transferred to a soft secondary matrix, as compared to soft-primed cells. This mechanical memory effect was mediated by the Yes-associated protein (YAP) and the microRNA-21 (miR-21) that are two mechanosensors initially identified as long-term memory keepers in mesenchymal stem cells. Soft-primed cells showed (i) a lower YAP nuclear translocation when transferred to a stiff secondary matrix and (ii) a loss of rigidity sensing through YAP, as compared to stiff-primed cells. The mechanical adaptation resulted in a differential expression ...Continue Reading

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Mentioned in this Paper

Pancreatic Carcinoma
Extracellular Matrix
Neoplasms
Mechanotransduction, Cellular
MIR21
MIR21 gene
Microscopy, Atomic Force
Site
Nuclear Translocation
Adaptation

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