Biophysical Society Thematic Meeting | Singapore

Mechanobiology of Disease

Poster Abstracts

40-POS Board 40 Caveolin-1 Phosphorylation Drives Elevated Hydrostatic Pressure-Induced Invasion of Lung Cancer Cells Yu-Chiu Kao 1,2 , Huei-Jyuan Pan 2 , Chau-Hwang Lee 2,3,4 , Po-Ling Kuo 1,5,6 . 1 National Taiwan University, Taipei, Taiwan, 2 Academia Sinica, Taipei, Taiwan, 3 National Yang-Ming University, Taipei, Taiwan, 4 National Taiwan University, Taipei, Taiwan, 5 National Taiwan University, Taipei, Taiwan, 6 National Taiwan University Hospital, Taipei, Taiwan. Most solid tumors are characterized by high interstitial fluid pressures (IFPs) that are uniformly distributed throughout the tumor yet the roles of the high IFP on the invasiveness of cancer cells remain unclear. Using three-dimensional transwell assays that were adapted for application of hydrostatic pressure (HP) to the cultured cells to simulate increased IFP conditions ranging from 0 to 20 mmHg, we found that the elevated HPs increased the invasiveness of lung cancer cells CL1-5 and A549. The migration speeds and volumes of the lung cancer cells were also significantly increased in the 20 mmHg HP condition. Biochemical analysis using Western blotting, protein phosphorylation inhibitors, and selected proteins knockdown with siRNA transfection revealed that the high IFP conditions induced caveolin-1 phosphorylation, which in turn promoted phosphorylation of Akt1/2 and subsequently ERK1/2, and the downstream expression of invasiveness markers including Snail, vinculin, aquaporin-1, as well as the phosphorylation of cortactin. Our results disclose a novel pathway relating high IFP to the invasiveness of cancer cells and highlight potential targets to hinder cancer cells spreading.

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