62 / 129
Mechanobiology of Disease
Poster Abstracts
57
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.