Nucleosome remodeler SNF2L suppresses cell proliferation and migration and attenuates Wnt signaling

Maren Eckey; Silke Kuphal; Tobias Straub; Petra Rümmele; Elisabeth Kremmer; Anja K Bosserhoff; Peter B Becker

doi:10.1128/MCB.06619-11

Nucleosome remodeler SNF2L suppresses cell proliferation and migration and attenuates Wnt signaling

Mol Cell Biol. 2012 Jul;32(13):2359-71. doi: 10.1128/MCB.06619-11. Epub 2012 Apr 16.

Authors

Maren Eckey¹, Silke Kuphal, Tobias Straub, Petra Rümmele, Elisabeth Kremmer, Anja K Bosserhoff, Peter B Becker

Affiliation

¹ Adolf Butenandt Institute, Center for Integrated Protein Science (CIPSM), Ludwig Maximilian University, Munich, Germany.

Abstract

ISWI is an evolutionarily conserved ATPase that catalyzes nucleosome remodeling in different macromolecular complexes. Two mammalian ISWI orthologs, SNF2H and SNF2L, are thought to have specialized functions despite their high sequence similarity. To date, the function of SNF2L in human cells has not been a focus of research. Newly established specific monoclonal antibodies and selective RNA interference protocols have now enabled a comprehensive characterization of loss-of-function phenotypes in human cells. In contrast to earlier results, we found SNF2L to be broadly expressed in primary human tissues. Depletion of SNF2L in HeLa cells led to enhanced proliferation and increased migration. These phenomena were explained by transcriptome profiling, which identified SNF2L as a modulator of the Wnt signaling network. The cumulative effects of SNF2L depletion on gene expression portray the cell in a state of activated Wnt signaling characterized by increased proliferation and chemotactic locomotion. Accordingly, high levels of SNF2L expression in normal melanocytes contrast with undetectable expression in malignant melanoma. In summary, our data document an inverse relationship between SNF2L expression and features characteristic of malignant cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenosine Triphosphatases / genetics
Adenosine Triphosphatases / metabolism
Antibodies, Monoclonal
Antibody Specificity
Base Sequence
Cell Adhesion / physiology
Cell Line, Tumor
Cell Movement / physiology*
Cell Proliferation*
Chromosomal Proteins, Non-Histone / genetics
Chromosomal Proteins, Non-Histone / metabolism
DNA-Binding Proteins / antagonists & inhibitors
DNA-Binding Proteins / genetics
DNA-Binding Proteins / immunology
DNA-Binding Proteins / metabolism*
Female
Gene Expression Profiling
Gene Knockdown Techniques
HeLa Cells
Humans
Male
Melanocytes / metabolism
Melanoma / genetics
Melanoma / metabolism
Melanoma / pathology
Nucleosomes / physiology*
RNA, Small Interfering / genetics
Tissue Distribution
Transcription Factors / antagonists & inhibitors
Transcription Factors / genetics
Transcription Factors / immunology
Transcription Factors / metabolism*
Wnt Signaling Pathway / physiology*
beta Catenin / genetics
beta Catenin / metabolism

Substances

Antibodies, Monoclonal
CTNNB1 protein, human
Chromosomal Proteins, Non-Histone
DNA-Binding Proteins
Nucleosomes
RNA, Small Interfering
SMARCA1 protein, human
Transcription Factors
beta Catenin
Adenosine Triphosphatases
SMARCA5 protein, human