Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING
GLOBETECH PUBLISHING
JIB

Signaling Protein Stabilizes Heterochromatin and Suppresses Tumor Growth

By BiotechDaily International staff writers
Posted on 20 Jun 2013
Genomics researchers have found that the unphosphorylated form of the STAT5A signaling protein functions as a tumor suppressor by stabilizing heterochromatin, which blocks the expression of multiple oncogenes.

STAT5A (signal transducer and activator of transcription 5A) is a member of the STAT protein family, which regulates many aspects of cell growth, survival, and differentiation. Disruption of this signaling pathway is frequently observed in primary tumors and leads to increased angiogenesis and enhanced tumor survival. Knockout studies have provided evidence that STAT proteins are involved in the development and function of the immune system, and play a role in maintaining immune tolerance and tumor surveillance. STAT5A is activated by and it mediates the responses of many cell ligands, such as interleukins and growth hormones.

Investigators at the University of California, San Diego School of Medicine (USA; www.ucsd.edu) and their colleagues at the University of Rochester Medical Center (NY, USA) worked with a mouse xenograft colon cancer model to study the effects of STAT5A.

They reported in the June 3, 2013, online edition of the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS) that unphosphorylated STAT5A bound to the heterochromatin protein 1-alpha (HP1-alpha) and stabilized the heterochromatin. Expressing unphosphorylated STAT5A or HP1-alpha inhibited colon cancer growth in the mouse xenograft model.

Previous experiments conducted in fruit flies had shown that the unphosphorylated form of STAT5A caused chromatin to condense into heterochromatin, while the phosphorylated form prompted dispersal and loss of heterochromatin, furthering gene expression.

“Unphosphorylated STAT promotes and stabilizes heterochromatin formation, which in turn suppresses gene transcription,” said senior author Dr. Willis X. Li, professor of medicine at the University of California, San Diego School of Medicine. “When we expressed either HP1-alpha (the central component of heterochromatin) or unphosphorylated STAT5A in human cancer cells, many genes important for cancer growth are suppressed. These cancer cells do not grow as fast or big as their control parental cancer cells in mouse xenograft models.”

Transcriptome profiling showed that expressing unphosphorylatable STAT5A had similar effects to overexpressing HP1-alpha in global gene expression. The majority of the genes commonly repressed by unphosphorylated STAT5A and HP1-alpha have been implicated in cancer development, and down regulation, somatic mutations, and deletions of STAT5 genes are found in certain human cancers.

“We are in the process of identifying small molecule drugs that may promote heterochromatin formation without stopping cell division or causing cell death,” said Dr. Li. “These drugs, if found, may be effective in treating cancers with fewer side effects.”

Related Links:
University of California, San Diego School of Medicine
University of Rochester Medical Center



comments powered by Disqus

Channels

Drug Discovery

view channel
Image: The five stages of biofilm development: (1) Initial attachment, (2) Irreversible attachment, (3) Maturation I, (4) Maturation II, and (5) Dispersion. Each stage of development in the diagram is paired with a photomicrograph of a developing P. aeruginosa biofilm. All photomicrographs are shown to same scale (Photo courtesy of Wikimedia Commons).

Ionic Liquids Disperse Bacterial Biofilms and Increase Antibiotic Susceptibility

The ionic liquid choline-geranate was shown to effectively eliminate the protective biofilm generated by bacteria such as Salmonella enterica and Pseudomonas aeruginosa and to significantly increase the... Read more

Therapeutics

view channel
Image: Hair follicle (blue) being attacked by T cells (green) (Photo courtesy of Christiano Lab/Columbia University Medical Center).

Hair Restoration Method Clones Patients’ Cells to Grow New Hair Follicles

Researchers have developed of a new hair restoration approach that uses a patient’s cells to grow new hair follicles. In addition, the [US] Food and Drugs Administration (FDA) recently approved a new drug... Read more

Lab Technologies

view channel
Image: Leica Microsystems launches the inverted research microscope platform Leica DMi8 (Photo courtesy of Leica Microsystems).

New Inverted Microscope Designed to Readily Adapt to Changing Research Demands

A new inverted microscope for biotech and other life science laboratories was designed to readily accommodate modifications and upgrades to allow it to keep current with changing research demands and interests.... Read more

Business

view channel

Partnership Established to Decode Bowel Disease

23andMe (Mountain View, CA,USA), a personal genetics company, is collaborating with Pfizer, Inc. (New York, NY, USA), in which the companies will seek to enroll 10,000 people with inflammatory bowel disease (IBD) in a research project designed to explore the genetic factors associated with the onset, progression, severity,... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.