title: SNAIL-induced epithelial-to-mesenchymal transition produces concerted biophysical changes from altered cytoskeletal gene expression.
abstract: A growing body of evidence suggests that the developmental process of epithelial-to-mesenchymal transition (EMT) is co-opted by cancer cells to metastasize to distant sites. This transition is associated with morphologic elongation and loss of cell-cell adhesions, though little is known about how it alters cell biophysical properties critical for migration. Here, we use multiple-particle tracking (MPT) microrheology and traction force cytometry to probe how genetic induction of EMT in epithelial MCF7 breast cancer cells changes their intracellular stiffness and extracellular force exertion, respectively, relative to an empty vector control. This analysis demonstrated that EMT alone was sufficient to produce dramatic cytoskeletal softening coupled with increases in cell-exerted traction forces. Microarray analysis revealed that these changes corresponded with down-regulation of genes associated with actin cross-linking and up-regulation of genes associated with actomyosin contraction. Finally, we show that this loss of structural integrity to expedite migration could inhibit mesenchymal cell proliferation in a secondary tumor as it accumulates solid stress. This work demonstrates that not only does EMT enable escape from the primary tumor through loss of cell adhesions but it also induces a concerted series of biophysical changes enabling enhanced migration of cancer cells after detachment from the primary tumor.
authors.affiliation: *School of Chemical & Biomolecular Engineering;School of Biology; and The Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: McGrail
authors.affiliation: *School of Chemical & Biomolecular Engineering;School of Biology; and The Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USA.
authors.forename: Roman
authors.initials: R
authors.lastname: Mezencev
authors.affiliation: *School of Chemical & Biomolecular Engineering;School of Biology; and The Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USA.
authors.forename: Quang Minh N
authors.initials: QM
authors.lastname: Kieu
authors.affiliation: *School of Chemical & Biomolecular Engineering;School of Biology; and The Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USA.
authors.forename: John F
authors.initials: JF
authors.lastname: McDonald
authors.affiliation: *School of Chemical & Biomolecular Engineering;School of Biology; and The Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USA mdawson@gatech.edu.
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Dawson
mesh_terms: D000199:Actins / Q000378:metabolism; D055592:Biophysical Phenomena; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D003599:Cytoskeleton / Q000235:genetics* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics* / Q000502:physiology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D061986:MCF-7 Cells; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D014170:Transformation, Genetic
chemical_list: D000199:Actins; D011994:Recombinant Proteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors
keywords: cell mechanics; metastasis; motility; physical oncology