Premium
Change in cell shape is required for matrix metalloproteinase‐induced epithelial‐mesenchymal transition of mammary epithelial cells
Author(s) -
Nelson Celeste M.,
Khauv Davitte,
Bissell Mina J.,
Radisky Derek C.
Publication year - 2008
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21821
Subject(s) - microbiology and biotechnology , epithelial–mesenchymal transition , cell , matrix metalloproteinase , biology , cell growth , mesenchymal stem cell , cytoskeleton , cell migration , cell signaling , extracellular matrix , matrix (chemical analysis) , chemistry , signal transduction , downregulation and upregulation , biochemistry , chromatography , gene
Cell morphology dictates response to a wide variety of stimuli, controlling cell metabolism, differentiation, proliferation, and death. Epithelial‐mesenchymal transition (EMT) is a developmental process in which epithelial cells acquire migratory characteristics, and in the process convert from a “cuboidal” epithelial structure into an elongated mesenchymal shape. We had shown previously that matrix metalloproteinase‐3 (MMP3) can stimulate EMT of cultured mouse mammary epithelial cells through a process that involves increased expression of Rac1b, a protein that stimulates alterations in cytoskeletal structure. We show here that cells treated with MMP‐3 or induced to express Rac1b spread to cover a larger surface, and that this induction of cell spreading is a requirement of MMP‐3/Rac1b‐induced EMT. We find that limiting cell spreading, either by increasing cell density or by culturing cells on precisely defined micropatterned substrata, blocks expression of characteristic markers of EMT in cells treated with MMP‐3. These effects are not caused by general disruptions in cell signaling pathways, as TGF‐β‐induced EMT is not affected by similar limitations on cell spreading. Our data reveal a previously unanticipated cell shape‐dependent mechanism that controls this key phenotypic alteration and provide insight into the distinct mechanisms activated by different EMT‐inducing agents. J. Cell. Biochem. 105: 25–33, 2008. © 2008 Wiley‐Liss, Inc.