PMID- 25698877 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20150220 LR - 20240322 IS - 1176-9351 (Print) IS - 1176-9351 (Electronic) IS - 1176-9351 (Linking) VI - 14 IP - Suppl 3 DP - 2015 TI - Regulation of epithelial-mesenchymal transition in breast cancer cells by cell contact and adhesion. PG - 1-13 LID - 10.4137/CIN.S18965 [doi] AB - Epithelial-mesenchymal transition (EMT) is a physiological program that is activated during cancer cell invasion and metastasis. We show here that EMT-related processes are linked to a broad and conserved program of transcriptional alterations that are influenced by cell contact and adhesion. Using cultured human breast cancer and mouse mammary epithelial cells, we find that reduced cell density, conditions under which cell contact is reduced, leads to reduced expression of genes associated with mammary epithelial cell differentiation and increased expression of genes associated with breast cancer. We further find that treatment of cells with matrix metalloproteinase-3 (MMP-3), an inducer of EMT, interrupts a defined subset of cell contact-regulated genes, including genes encoding a variety of RNA splicing proteins known to regulate the expression of Rac1b, an activated splice isoform of Rac1 known to be a key mediator of MMP-3-induced EMT in breast, lung, and pancreas. These results provide new insights into how MMPs act in cancer progression and how loss of cell-cell interactions is a key step in the earliest stages of cancer development. FAU - Cichon, Magdalena A AU - Cichon MA AD - Department of Cancer Biology, Mayo Clinic Cancer Center, Jacksonville, FL USA. FAU - Nelson, Celeste M AU - Nelson CM AD - Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ, USA. ; Department of Molecular Biology, Princeton University, Princeton, NJ, USA. FAU - Radisky, Derek C AU - Radisky DC AD - Department of Cancer Biology, Mayo Clinic Cancer Center, Jacksonville, FL USA. LA - eng GR - R21 HL110335/HL/NHLBI NIH HHS/United States GR - R21 HL118532/HL/NHLBI NIH HHS/United States GR - R01 GM083997/GM/NIGMS NIH HHS/United States GR - R01 HL120142/HL/NHLBI NIH HHS/United States GR - P50 CA116201/CA/NCI NIH HHS/United States PT - Journal Article DEP - 20150209 PL - United States TA - Cancer Inform JT - Cancer informatics JID - 101258149 PMC - PMC4325704 OTO - NOTNLM OT - breast cancer OT - cell contact OT - epithelial-mesenchymal transition OT - extracellular matrix OT - mammary epithelial cells OT - matrix metalloproteinases EDAT- 2015/02/24 06:00 MHDA- 2015/02/24 06:01 PMCR- 2015/02/09 CRDT- 2015/02/21 06:00 PHST- 2014/11/25 00:00 [received] PHST- 2014/12/29 00:00 [revised] PHST- 2015/01/04 00:00 [accepted] PHST- 2015/02/21 06:00 [entrez] PHST- 2015/02/24 06:00 [pubmed] PHST- 2015/02/24 06:01 [medline] PHST- 2015/02/09 00:00 [pmc-release] AID - cin-suppl.3-2015-001 [pii] AID - 10.4137/CIN.S18965 [doi] PST - epublish SO - Cancer Inform. 2015 Feb 9;14(Suppl 3):1-13. doi: 10.4137/CIN.S18965. eCollection 2015.