Epithelial-mesenchymal transition enhances nanoscale actin filament dynamics of ovarian cancer cells

Sunyoung Lee, Yang Yang, David Fishman, Mark M. Banaszak Holl, Seungpyo Hong

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Epithelial ovarian cancer cells enhance their ability to migrate and invade through the epithelial-mesenchymal transition (EMT), resulting in cell seeding and metastasis in the peritoneal cavity and onto adjacent organ surfaces. It has been speculated that cytoskeletal dynamics, such as those of the actin filament, play a role in enhanced cell motility; however, direct evidence has not been provided. Herein, we have directly measured pico- to nanonewton-scale mechanical forces generated by actin dynamics of ovarian cancer SKOV-3 cells upon binding of integrin α5β1 to fibronectin (FN), i.e., formation of a focal adhesion, using real-time atomic force microscopy (AFM) in a force spectroscopy mode. The dendrimer surface chemistry through which FN was immobilized on the AFM probe surfaces further enhanced the sensitivity of the force measurement by 1.5-fold. Post-EMT SKOV-3 cells, induced by transforming growth factor-β, generated larger focal adhesion mechanical forces (17 and 41 nN before and after EMT, respectively) with migration faster than that of pre-EMT cells. Importantly, 22% of the forces transmitted through a single FN-integrin α5β1 pair from post-EMT cells were shown to be sufficient to rupture the binding between FN and integrin α5β1 on the cells, a result which is not observed on pre-EMT cells. This implies that post-EMT cells, by generating forces strong enough to break the FN-integrin binding, migrate and metastasize beyond the ovary, whereas pre-EMT cancer cells are confined in the ovary without such force generation. These results demonstrate quantitative and direct evidence for the role of actin dynamics in the enhanced motility of post-EMT ovarian cancer cells, providing a fundamental insight into the mechanism of ovarian cancer metastasis.

Original languageEnglish
Pages (from-to)9233-9240
Number of pages8
JournalJournal of Physical Chemistry B
Volume117
Issue number31
DOIs
Publication statusPublished - 2013 Aug 8

Fingerprint

Fibronectins
Actins
filaments
Integrins
cancer
Cells
Atomic force microscopy
Adhesion
cells
Force measurement
Dendrimers
Surface chemistry
ovaries
locomotion
Spectroscopy
metastasis
Transforming Growth Factors
adhesion
atomic force microscopy
dendrimers

All Science Journal Classification (ASJC) codes

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry

Cite this

Lee, Sunyoung ; Yang, Yang ; Fishman, David ; Banaszak Holl, Mark M. ; Hong, Seungpyo. / Epithelial-mesenchymal transition enhances nanoscale actin filament dynamics of ovarian cancer cells. In: Journal of Physical Chemistry B. 2013 ; Vol. 117, No. 31. pp. 9233-9240.
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abstract = "Epithelial ovarian cancer cells enhance their ability to migrate and invade through the epithelial-mesenchymal transition (EMT), resulting in cell seeding and metastasis in the peritoneal cavity and onto adjacent organ surfaces. It has been speculated that cytoskeletal dynamics, such as those of the actin filament, play a role in enhanced cell motility; however, direct evidence has not been provided. Herein, we have directly measured pico- to nanonewton-scale mechanical forces generated by actin dynamics of ovarian cancer SKOV-3 cells upon binding of integrin α5β1 to fibronectin (FN), i.e., formation of a focal adhesion, using real-time atomic force microscopy (AFM) in a force spectroscopy mode. The dendrimer surface chemistry through which FN was immobilized on the AFM probe surfaces further enhanced the sensitivity of the force measurement by 1.5-fold. Post-EMT SKOV-3 cells, induced by transforming growth factor-β, generated larger focal adhesion mechanical forces (17 and 41 nN before and after EMT, respectively) with migration faster than that of pre-EMT cells. Importantly, 22{\%} of the forces transmitted through a single FN-integrin α5β1 pair from post-EMT cells were shown to be sufficient to rupture the binding between FN and integrin α5β1 on the cells, a result which is not observed on pre-EMT cells. This implies that post-EMT cells, by generating forces strong enough to break the FN-integrin binding, migrate and metastasize beyond the ovary, whereas pre-EMT cancer cells are confined in the ovary without such force generation. These results demonstrate quantitative and direct evidence for the role of actin dynamics in the enhanced motility of post-EMT ovarian cancer cells, providing a fundamental insight into the mechanism of ovarian cancer metastasis.",
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Epithelial-mesenchymal transition enhances nanoscale actin filament dynamics of ovarian cancer cells. / Lee, Sunyoung; Yang, Yang; Fishman, David; Banaszak Holl, Mark M.; Hong, Seungpyo.

In: Journal of Physical Chemistry B, Vol. 117, No. 31, 08.08.2013, p. 9233-9240.

Research output: Contribution to journalArticle

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