Unphosphorylated STAT5A stabilizes heterochromatin and suppresses tumor growth.

Abstract

Tumor suppressors known to date impede cancer growth by arresting the cell cycle or promoting apoptosis. Here we show that unphosphorylated human STAT5A functions as a tumor suppressor capable of repressing multiple oncogenes via heterochromatin formation. Unphosphorylated STAT5A binds to heterochromatin protein 1α (HP1α) and stabilizes heterochromatin. Expressing unphosphorylated STAT5A or HP1α inhibits colon cancer growth in mouse xenograft models. Transcriptome profiling shows that expressing an unphosphorylatable STAT5A has similar effects to overexpressing HP1α in global gene expression. Notably, the majority of the genes commonly repressed by unphosphorylated STAT5A and HP1α have been implicated in cancer development. Finally, down-regulation, somatic mutations, and deletions of STAT5 genes are found in certain human cancers. These results suggest that unphosphorylated STAT5A may epigenetically suppress tumor growth by promoting heterochromatin formation.

• Authors: Xiaoyu Hu, Pranabananda Dutta, Amy Tsurumi, Jinghong Li, Jingtong Wang, Hartmut Land, Willis X Li
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 110 Issue 25 Pg. 10213-8 (Jun 18 2013) ISSN: 1091-6490 [Electronic] United States
• PMID: 23733954 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• CBX5 protein, human
• Chromosomal Proteins, Non-Histone
• Heterochromatin
• RNA, Small Interfering
• STAT5 Transcription Factor
• STAT5A protein, human
• Tumor Suppressor Proteins
• Chromobox Protein Homolog 5

Topics

• Animals
• Cell Nucleus (metabolism)
• Cell Proliferation (drug effects)
• Chromobox Protein Homolog 5
• Chromosomal Proteins, Non-Histone (genetics, metabolism, pharmacology)
• Colonic Neoplasms (drug therapy, metabolism, pathology)
• Databases, Genetic
• Down-Regulation (genetics)
• Gene Expression Regulation, Neoplastic (drug effects, physiology)
• HEK293 Cells
• HeLa Cells
• Heterochromatin (metabolism)
• Humans
• Mice
• Phosphorylation (physiology)
• RNA, Small Interfering (genetics)
• STAT5 Transcription Factor (genetics, metabolism, pharmacology)
• Signal Transduction (physiology)
• Transcriptome
• Tumor Suppressor Proteins (genetics, metabolism, pharmacology)
• Xenograft Model Antitumor Assays