A transcriptional program mediating entry into cellular quiescence.
The balance of quiescence and cell division is critical for tissue homeostasis and organismal health. Serum stimulation of fibroblasts is well studied as a classic model of entry into the cell division cycle, but the induction of cellular quiescence, such as by serum deprivation (SD), is much less understood. Here we show that SS and SD activate distinct early transcriptional responses genome-wide that converge on a late symmetric transcriptional program. Several serum deprivation early response genes (SDERGs), including the putative tumor suppressor genes SALL2 and MXI1, are required for cessation of DNA synthesis in response to SD and induction of additional SD genes. SDERGs are coordinately repressed in many types of human cancers compared to their normal counterparts, and repression of SDERGs predicts increased risk of cancer progression and death in human breast cancers. These results identify a gene expression program uniquely responsive to loss of growth factor signaling; members of SDERGs may constitute novel growth inhibitors that prevent cancer.
Liu
Helen
H
Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California, United States of America.
Adler
Adam S
AS
Segal
Eran
E
Chang
Howard Y
HY
D001943:Breast Neoplasms / Q000473:pathology; D002453:Cell Cycle; D002455:Cell Division; D016922:Cellular Senescence; D018450:Disease Progression; D005347:Fibroblasts / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D012306:Risk; D015398:Signal Transduction; D014158:Transcription, Genetic