
Retinoblastoma protein (Rb) links hypoxia to altered mechanical properties in cancer cells as measured by an optical tweezer
Author(s) -
Samaneh Khakshour,
Mark P. Labrecque,
Hadi Esmaeilsabzali,
Frank J.S. Lee,
Michael Cox,
E. J. Park,
Timothy V. Beischlag
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-017-07947-6
Subject(s) - pi3k/akt/mtor pathway , protein kinase b , microbiology and biotechnology , cancer cell , hypoxia (environmental) , retinoblastoma protein , actin cytoskeleton , retinoblastoma , motility , chemistry , lncap , mapk/erk pathway , kinase , cancer research , signal transduction , biology , cell , cytoskeleton , cancer , cell cycle , biochemistry , organic chemistry , oxygen , gene , genetics
Hypoxia modulates actin organization via multiple pathways. Analyzing the effect of hypoxia on the biophysical properties of cancer cells is beneficial for studying modulatory signalling pathways by quantifying cytoskeleton rearrangements. We have characterized the biophysical properties of human LNCaP prostate cancer cells that occur in response to loss of the retinoblastoma protein (Rb) under hypoxic stress using an oscillating optical tweezer. Hypoxia and Rb-loss increased cell stiffness in a fashion that was dependent on activation of the extracellular signal-regulated kinase (ERK) and the protein kinase B (AKT)- mammalian target of rapamycin (MTOR) pathways. Pharmacological inhibition of MEK1/2, AKT or MTOR impeded hypoxia-inducible changes in the actin cytoskeleton and inhibited cell migration in Rb-deficient cells conditioned with hypoxia. These results suggest that loss of Rb in transformed hypoxic cancer cells affects MEK1/2-ERK/AKT-MTOR signalling and promotes motility. Thus, the mechanical characterization of cancer cells using an optical tweezer provides an additional technique for cancer diagnosis/prognosis and evaluating therapeutic performance.