Researchers from Mount Sinai's Icahn School of Medicine have found that altering the structure of a protein histone called H3.3 plays a significant role in disrupting genes responsible for regulating the growth of cancer cells.
Published in the journal Nature Communications, the study is the first to identify the H3.3 protein as a key regulator for cellular senescence or the process in which cells stop multiplying. There is little known about how cellular senescence is carried out but it has generated interest in the scientific community because of its potential in cancer treatment. There is growing evidence, though that the process is mostly driven by changes in chromatin or the protein complexes in cell nuclei.
With the help of senescence models, researchers discovered that H3.3 can be used to help stop targeted genes responsible for certain processes in the cell cycle. Genome-wide transcriptional profiling allowed the researchers to see that clipping H3.3 from the sequence disrupts gene activity aimed at dividing and duplicating a cell.
"Cellular senescence creates a chromatin environment that represses cell multiplication, and thus cell or tumor growth, but how this happens molecularly is what we sought to discover," said Emily Bernstein, Ph.D., from the department of oncological sciences from the Icahn School of Medicine at Mount Sinai and the study's lead investigator.
Instead, researchers found that H3.3 and the clipped form of the protein, which doesn't have 23 amino acids from the histone tail and the modifications associated with them, can prevent healthy cells from undergoing division. If clipped H3.3 is a marker for healthy cells to stop growing, it is implied then that the same could be said for cancer cells. This means the potential to halt cancer growths exists, most especially in the types of cancer that feature senescence.
According to the American Cancer Society, 310,010 men and 275,710 women are estimated to die from various types of cancer in 2014. The discovery of a protein that essentially acts like an "off switch" for cancer growth is likely to affect mortality rates due to cancer in the coming years.
This study received funding support from the National Cancer Institute, University of Cambridge, Hutchinson Whampoa, Human Frontier Science Program, and Cancer Research UK, as well as The Ellison Medical Foundation and Mount Sinai's Developmental Research Pilot Project Program.
Other investigators include Luis Duarte, Masashi Narita, Andrew R. J. Young, Avi Ma'ayan, Zichen Wang, Nicholas Mills, Hsan-Au Wu, Dan Hasson, Taniya Panda, Avnish Kapoor and Yan Kou.
