June 2, 2014 13:10 — 0 Comments
Study Identifies New Way Brain Tumors Become More Malignant
Researchers at the University of Alabama at Birmingham have identified a strategy that highly aggressive brain tumor cells use to fuel their relentless expansion. In a study recently published online in The Journal of Clinical Investigation, the research team demonstrates that alternative splicing, or the beading together of different parts of a gene, allows brain tumors to incapacitate a key tumor suppressor gene, and that this splicing event happens in a tissue-specific context. The team discovered that a specific spliced form of the membrane-binding tumor suppressor annexin A7, or ANXA7, leads to the decreased breakdown of a receptor, EGFR, that contributes to the growth of tumor cells. The study reveals what happens to ANXA7 — and introduces a fresh target for cancer therapy: PTBP1. This “splice factor” snips out a crucial part of the ANXA7 gene, compromising its function. The researchers found that in the brain this process happens in stemlike precursor cells that represent potential cells of origin of glioblastoma but not in mature neuronal cells. The research team demonstrated that PTBP1 is overexpressed in animal models of glioblastoma; they also found the same thing in tissue samples from human patients. “We showed that when you have elevated PTBP1 levels in a tumor, brought about in part by amplification of the PTBP1 gene, it portends the worst prognosis for the patients,” said Markus Bredel, MD, PhD, professor in the UAB Department of Radiation Oncology. To learn more about this study, click here.