Cell competition in mouse NIH3T3 embryonic fibroblasts is controlled by the activity of Tead family proteins and Myc

Hiroshi Mamada; Takashi Sato; Mitsunori Ota; Hiroshi Sasaki

doi:10.1242/jcs.163675

Cell competition in mouse NIH3T3 embryonic fibroblasts is controlled by the activity of Tead family proteins and Myc

J Cell Sci. 2015 Feb 15;128(4):790-803. doi: 10.1242/jcs.163675. Epub 2015 Jan 14.

Authors

Hiroshi Mamada¹, Takashi Sato¹, Mitsunori Ota¹, Hiroshi Sasaki²

Affiliations

¹ Department of Cell Fate Control, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Kumamoto 860-0811, Japan.
² Department of Cell Fate Control, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Kumamoto 860-0811, Japan [email protected].

PMID: 25588835
DOI: 10.1242/jcs.163675

Abstract

Cell competition is a short-range communication originally observed in Drosophila. Relatively little is known about cell competition in mammals or in non-epithelial cells. Hippo signaling and its downstream transcription factors of the Tead family, control cell proliferation and apoptosis. Here, we established an in vitro model system that shows cell competition in mouse NIH3T3 embryo fibroblast cells. Co-culture of Tead-activity-manipulated cells with normal (wild-type) cells caused cell competition. Cells with reduced Tead activity became losers, whereas cells with increased Tead activity became super-competitors. Tead directly regulated Myc RNA expression, and cells with increased Myc expression also became super-competitors. At low cell density, cell proliferation required both Tead activity and Myc. At high cell density, however, reduction of either Tead activity or Myc was compensated for by an increase in the other, and this increase was sufficient to confer 'winner' activity. Collectively, NIH3T3 cells have cell competition mechanisms similar to those regulated by Yki and Myc in Drosophila. Establishment of this in vitro model system should be useful for analyses of the mechanisms of cell competition in mammals and in fibroblasts.

Keywords: Cell competition; Myc; NIH3T3 cells; Tead.

Publication types

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

MeSH terms

3T3 Cells
Adaptor Proteins, Signal Transducing / antagonists & inhibitors
Adaptor Proteins, Signal Transducing / metabolism
Animals
Apoptosis / genetics*
Caspase 3 / metabolism
Cell Communication / genetics
Cell Communication / physiology*
Cell Cycle Proteins
Cell Line
Cell Proliferation / genetics
Cysteine-Rich Protein 61 / metabolism
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism*
Drosophila / metabolism
Drosophila Proteins / metabolism
Enzyme Activation / genetics
Fibroblasts
Hippo Signaling Pathway
Mice
Nuclear Proteins / metabolism
Phosphoproteins / antagonists & inhibitors
Phosphoproteins / metabolism
Protein Serine-Threonine Kinases / metabolism
Proto-Oncogene Proteins c-myc / genetics
Proto-Oncogene Proteins c-myc / metabolism*
RNA Interference
RNA, Messenger / biosynthesis
RNA, Small Interfering
Signal Transduction / genetics
TEA Domain Transcription Factors
Trans-Activators / metabolism
Transcription Factors / genetics
Transcription Factors / metabolism*
YAP-Signaling Proteins

Substances

Adaptor Proteins, Signal Transducing
CCN1 protein, mouse
Cell Cycle Proteins
Cysteine-Rich Protein 61
DNA-Binding Proteins
Drosophila Proteins
Myc protein, mouse
Nuclear Proteins
Phosphoproteins
Proto-Oncogene Proteins c-myc
RNA, Messenger
RNA, Small Interfering
TEA Domain Transcription Factors
Tead1 protein, mouse
Tead2 protein, mouse
Trans-Activators
Transcription Factors
YAP-Signaling Proteins
Yap1 protein, mouse
Yki protein, Drosophila
Protein Serine-Threonine Kinases
Caspase 3