Positive Quantitative Relationship between EMT and Contact-Initiated Sliding on Fiber-like Tracks

Biophysical Journal
Daniel F MilanoAnand R Asthagiri

Abstract

Epithelial-mesenchymal transition (EMT) is a complex process by which cells acquire invasive properties that enable escape from the primary tumor. Complete EMT, however, is not required for metastasis: circulating tumor cells exhibit hybrid epithelial-mesenchymal states, and genetic perturbations promoting partial EMT induce metastasis in vivo. An open question is whether and to what extent intermediate stages of EMT promote invasiveness. Here, we investigate this question, building on recent observation of a new invasive property. Migrating cancer cell lines and cells transduced with prometastatic genes slide around other cells on spatially confined, fiberlike micropatterns. We show here that low-dosage/short-duration exposure to transforming growth factor beta (TGFβ) induces partial EMT and enables sliding on narrower (26 μm) micropatterns than untreated counterparts (41 μm). High-dosage/long-duration exposure induces more complete EMT, including disrupted cell-cell contacts and reduced E-cadherin expression, and promotes sliding on the narrowest (15 μm) micropatterns. These results identify a direct and quantitative relationship between EMT and cell sliding and show that EMT-associated invasive sliding is progressive, with c...Continue Reading

Citations

Aug 22, 2002·Nature Reviews. Cancer·J P Thiery
Nov 19, 2004·Neoplasia : an International Journal for Oncology Research·Lu XieHarold L Moses
Dec 28, 2006·BMC Medicine·Paolo P ProvenzanoPatricia J Keely
Jun 15, 2007·Pathology·Marcello GuarinoGianmario Ballabio
May 17, 2008·Cancer Research·Tamer T OnderRobert A Weinberg
Jul 30, 2008·Cell·Joan Massagué
Dec 1, 2009·Cell·J P ThieryM Angela Nieto
Mar 26, 2011·Science·Christine L Chaffer, Robert A Weinberg
Jun 15, 2011·Molecular Cancer Research : MCR·Andrew J ArmstrongMariano A Garcia-Blanco
Feb 9, 2012·Langmuir : the ACS Journal of Surfaces and Colloids·Keiichiro Kushiro, Anand R Asthagiri
Dec 15, 2012·Cancer Cell·Thomas Brabletz
Dec 19, 2012·Proceedings of the National Academy of Sciences of the United States of America·Hui WangSenthil K Muthuswamy
Jan 23, 2013·Breast Cancer Research and Treatment·Antoinette HollestelleJohn W M Martens
Oct 25, 2013·Proceedings of the National Academy of Sciences of the United States of America·Mingyang LuEshel Ben-Jacob
Feb 22, 2014·Nature Reviews. Molecular Cell Biology·Samy LamouilleRik Derynck
Apr 28, 2016·Biophysical Journal·Daniel F MilanoAnand R Asthagiri

Related Concepts

In Vivo
Patterns
Transforming Growth Factor beta
MRNA Maturation
TGFA protein, human
Genes
Cell Motility
Meso-epithelial Cell
Neoplastic Cell
Primary Neoplasm

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