PMID- 23660532 OWN - NLM STAT- MEDLINE DCOM- 20140502 LR - 20220223 IS - 1432-0436 (Electronic) IS - 0301-4681 (Print) IS - 0301-4681 (Linking) VI - 86 IP - 3 DP - 2013 Oct TI - Extracellular matrix proteins regulate epithelial-mesenchymal transition in mammary epithelial cells. PG - 126-32 LID - S0301-4681(13)00025-X [pii] LID - 10.1016/j.diff.2013.03.003 [doi] AB - Mouse mammary epithelial cells undergo transdifferentiation via epithelial-mesenchymal transition (EMT) upon treatment with matrix metalloproteinase-3 (MMP3). In rigid microenvironments, MMP3 upregulates expression of Rac1b, which translocates to the cell membrane to promote induction of reactive oxygen species and EMT. Here we examine the role of the extracellular matrix (ECM) in this process. Our data show that the basement membrane protein laminin suppresses the EMT response in MMP3-treated cells, whereas fibronectin promotes EMT. These ECM proteins regulate EMT via interactions with their specific integrin receptors. alpha6-integrin sequesters Rac1b from the membrane and is required for inhibition of EMT by laminin. In contrast, alpha5-integrin maintains Rac1b at the membrane and is required for the promotion of EMT by fibronectin. Understanding the regulatory role of the ECM will provide insight into mechanisms underlying normal and pathological development of the mammary gland. CI - (c) 2013 International Society of Differentiation. Published by Elsevier B.V. All rights reserved. FAU - Chen, Qike K AU - Chen QK AD - Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA. FAU - Lee, KangAe AU - Lee K FAU - Radisky, Derek C AU - Radisky DC FAU - Nelson, Celeste M AU - Nelson CM LA - eng GR - R21 HL110335/HL/NHLBI NIH HHS/United States GR - HL110335/HL/NHLBI NIH HHS/United States GR - R01 GM083997/GM/NIGMS NIH HHS/United States GR - CA128660/CA/NCI NIH HHS/United States GR - R21 CA128660/CA/NCI NIH HHS/United States GR - GM083997/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20130506 PL - England TA - Differentiation JT - Differentiation; research in biological diversity JID - 0401650 RN - 0 (Fibronectins) RN - 0 (Integrin alpha5) RN - 0 (Integrin alpha6) RN - 0 (Laminin) RN - 0 (Neuropeptides) RN - 0 (Rac1 protein, mouse) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) RN - EC 3.4.24.17 (Mmp3 protein, mouse) RN - EC 3.6.5.2 (rac1 GTP-Binding Protein) SB - IM MH - Animals MH - Cell Line MH - Epithelial Cells/*drug effects/metabolism/physiology MH - Epithelial-Mesenchymal Transition/*drug effects MH - Extracellular Space/metabolism MH - Female MH - Fibronectins/*pharmacology MH - Integrin alpha5/genetics/metabolism MH - Integrin alpha6/genetics/metabolism MH - Laminin/*pharmacology MH - Mammary Glands, Animal/*cytology MH - Matrix Metalloproteinase 3/*pharmacology MH - Mice MH - Neuropeptides/genetics/metabolism MH - Stress, Mechanical MH - rac1 GTP-Binding Protein/genetics/metabolism PMC - PMC3762919 MID - NIHMS469160 OTO - NOTNLM OT - Alpha-smooth muscle actin OT - BM OT - Basement membrane OT - Cell shape OT - ECM OT - EMT OT - EMyT OT - Epithelial-mesenchymal transition OT - Epithelial-myofibroblast transition OT - Extracellular matrix OT - Integrin OT - Laminin-rich ECM OT - MMP3 OT - Matrix metalloproteinase-3 OT - Mechanical stress OT - ROS OT - Reactive oxygen species OT - TGFbeta OT - Transforming growth factor-beta OT - lrECM OT - alphaSMA EDAT- 2013/05/11 06:00 MHDA- 2014/05/03 06:00 PMCR- 2014/10/01 CRDT- 2013/05/11 06:00 PHST- 2012/12/20 00:00 [received] PHST- 2013/03/20 00:00 [accepted] PHST- 2013/05/11 06:00 [entrez] PHST- 2013/05/11 06:00 [pubmed] PHST- 2014/05/03 06:00 [medline] PHST- 2014/10/01 00:00 [pmc-release] AID - S0301-4681(13)00025-X [pii] AID - 10.1016/j.diff.2013.03.003 [doi] PST - ppublish SO - Differentiation. 2013 Oct;86(3):126-32. doi: 10.1016/j.diff.2013.03.003. Epub 2013 May 6.