Inducible changes in cell size and attachment area due to expression of a mutant SWI/SNF chromatin remodeling enzyme.
The SWI/SNF enzymes belong to a family of ATP-dependent chromatin remodeling enzymes that have been functionally implicated in gene regulation, development, differentiation and oncogenesis. BRG1, the catalytic core subunit of some of the SWI/SNF enzymes, can interact with known tumor suppressor proteins and can act as a tumor suppressor itself. We report that cells that inducibly express ATPase-deficient versions of BRG1 increase in cell volume, area of attachment and nuclear size upon expression of the mutant BRG1 protein. Examination of focal adhesions reveals qualitative changes in paxillin distribution but no difference in the actin cytoskeletal structure. Increases in cell size and shape correlate with over-expression of two integrins and the urokinase-type plasminogen activator receptor (uPAR), which is also involved in cell adhesion and is often over-expressed in metastatic cancer cells. These findings demonstrate that gene expression pathways affected by chromatin remodeling enzymes can regulate the physical dimensions of mammalian cell morphology.
Hill
David A
DA
Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
Chiosea
Simion
S
Jamaluddin
Saha
S
Roy
Kanaklata
K
Fischer
Andrew H
AH
Boyd
Douglas D
DD
Nickerson
Jeffrey A
JA
Imbalzano
Anthony N
AN
D000199:Actins / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000737:chemistry; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002448:Cell Adhesion; D002454:Cell Differentiation; D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D048429:Cell Size; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism*; D003094:Collagen / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D004265:DNA Helicases; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D022001:Focal Adhesions / Q000378:metabolism; D005786:Gene Expression Regulation; D006579:Heterozygote; D006801:Humans; D007797:Laminin / Q000494:pharmacology; D051379:Mice; D009154:Mutation; D009362:Neoplasm Metastasis; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D051419:Paxillin; D010750:Phosphoproteins / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011509:Proteoglycans / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D013997:Time Factors; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*
D000199:Actins; D002843:Chromatin; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D004338:Drug Combinations; D007797:Laminin; D009687:Nuclear Proteins; C524898:PLAUR protein, human; C496061:PXN protein, human; D051419:Paxillin; D010750:Phosphoproteins; C524899:Plaur protein, mouse; D011509:Proteoglycans; C496062:Pxn protein, mouse; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014157:Transcription Factors; C059485:matrigel; D000255:Adenosine Triphosphate; D003094:Collagen; D000251:Adenosine Triphosphatases; C084108:SMARCA4 protein, human; C513194:Smarca4 protein, mouse; D004265:DNA Helicases