Potential New Way to Suppress Tumor Growth Discovered
Researchers at the University of California, San Diego, School of Medicine, and University of Rochester Medical Center have identified a new mechanism that appears to suppress tumor growth, opening the possibility of developing a new class of anticancer drugs. The findings were published in this week’s online Early Edition of the Proceedings of the National Academy of Sciences.
Role of STAT5A
According to Willis X. Li, PhD, Professor in the Department of Medicine at UC San Diego, a particular form of the STAT5A signaling protein stabilizes the formation of heterochromatin, which in turn suppresses the ability of cancer cells to issue instructions to multiply and grow.
Specifically, Dr. Li and colleagues found that the unphosphorylated form of STAT promotes and stabilizes heterochromatin, which keeps DNA tightly packaged and inaccessible to transcription factors. “Therefore, genes ‘buried’ in heterochromatin are not expressed,” explained Dr. Li.
Dr. Li said that in previous studies with fruit flies, the unphosphorylated form of STAT caused chromatin to condense into heterochromatin, while the phosphorylated version prompted dispersal and loss of heterochromatin, furthering gene expression.
“When we expressed either HP1 (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,” he said.
New Class of Tumor Suppressors?
Most of the known tumor suppressors, such as p53 or Rb, function by inhibiting cell-cycle progression or by spurring cell death, or apoptosis. Dr. Li said their findings reveal a potential new way to inhibit cancer gene expression, and may represent a new class of tumor suppressors.
“We are in the process of identifying small-molecule drugs that may promote heterochromatin formation without stopping cell division or causing cell death,” he said. “These drugs, if found, may be effective in treating cancers with fewer side effects.”
Funding for this research came, in part, from the National Institutes of Health grants R01CA131326 and RO1CA138249 and a Leukemia & Lymphoma Society Research Scholar grant. Dr. Li reported no potential conflicts of interest.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
