PMID- 18506791 OWN - NLM STAT- MEDLINE DCOM- 20081027 LR - 20220223 IS - 1097-4644 (Electronic) IS - 0730-2312 (Print) IS - 0730-2312 (Linking) VI - 105 IP - 1 DP - 2008 Sep 1 TI - Change in cell shape is required for matrix metalloproteinase-induced epithelial-mesenchymal transition of mammary epithelial cells. PG - 25-33 LID - 10.1002/jcb.21821 [doi] AB - 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-beta-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. CI - (c) 2008 Wiley-Liss, Inc. FAU - Nelson, Celeste M AU - Nelson CM AD - Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA. celesten@princeton.edu FAU - Khauv, Davitte AU - Khauv D FAU - Bissell, Mina J AU - Bissell MJ FAU - Radisky, Derek C AU - Radisky DC LA - eng GR - R37 CA064786/CA/NCI NIH HHS/United States GR - CA122086/CA/NCI NIH HHS/United States GR - CA128660/CA/NCI NIH HHS/United States GR - R21 CA128660/CA/NCI NIH HHS/United States GR - R01 CA057621-08/CA/NCI NIH HHS/United States GR - R01 CA057621/CA/NCI NIH HHS/United States GR - CA64786/CA/NCI NIH HHS/United States GR - R01 CA064786-08/CA/NCI NIH HHS/United States GR - CA57621/CA/NCI NIH HHS/United States GR - R01 CA064786/CA/NCI NIH HHS/United States GR - R01 CA122086/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. PL - United States TA - J Cell Biochem JT - Journal of cellular biochemistry JID - 8205768 RN - 0 (Transforming Growth Factor beta) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) SB - IM MH - Animals MH - *Cell Differentiation/drug effects MH - Cell Line MH - Cell Shape MH - Epithelial Cells/*cytology/*enzymology MH - Gene Expression Regulation, Enzymologic MH - Mammary Glands, Animal/*cytology/*enzymology MH - Matrix Metalloproteinase 3/genetics/*metabolism MH - Mesenchymal Stem Cells/cytology/*enzymology MH - Mice MH - Transforming Growth Factor beta/pharmacology PMC - PMC2838485 MID - NIHMS160561 EDAT- 2008/05/29 09:00 MHDA- 2008/10/28 09:00 PMCR- 2010/03/15 CRDT- 2008/05/29 09:00 PHST- 2008/05/29 09:00 [pubmed] PHST- 2008/10/28 09:00 [medline] PHST- 2008/05/29 09:00 [entrez] PHST- 2010/03/15 00:00 [pmc-release] AID - 10.1002/jcb.21821 [doi] PST - ppublish SO - J Cell Biochem. 2008 Sep 1;105(1):25-33. doi: 10.1002/jcb.21821.