Study finds some aggressive tumors silence genes that fight cancer

July 22, 2014 by Vicky Agnew
Study finds some aggressive tumors silence genes that fight cancer
When oxygen levels (shown as red balls) are low, DNA (shown in light blue) is frozen — and its gene expression, including that of tumor suppressors, is silenced.

(Medical Xpress)—A study led by Yale Cancer Center may provide clues to how some aggressive cancers turn off, or silence, genes critical to suppressing tumors. The findings, published in the journal Cell Reports, suggest that this gene silencing process could be interrupted to increase the chances that aggressive tumors will respond to treatment.

As cancer develops, it often outstrips its blood supply and receives less oxygen than normal tissue. This low-oxygen environment, called , is associated with of all types that are more likely to progress despite chemotherapy and radiation therapy.

The study, which used colon cancer tissue, found that hypoxia also triggers the silencing of a critical -suppressing gene called MLH1.

The team also identified an enzyme, LSD1 (lysine specific demethylase), associated with MLH1 that could be a target to reverse or block the silencing process. Since LSDI is an enzyme, it is possible to target it with small molecules to inhibit its activity.

"We've long known that hypoxic tumors are associated with worse prognoses, but the idea that hypoxic tumors could silence genes was an unexpected finding," said senior author Dr. Peter M. Glazer, the Robert H. Hunter Professor and chair of therapeutic radiology, and professor of genetics at Yale School of Medicine. "Now that we know how big a role hypoxia plays, we have a new and clinically-relevant path to explore in terms of circumventing this process. The next step is to determine how hypoxia affects other tumor-suppressing genes."

Explore further: Breast cancer tumor suppressor gene silenced by low O2

Related Stories

Breast cancer tumor suppressor gene silenced by low O2

August 16, 2011

Low oxygen can silence the BRCA1 tumor suppressor gene and contribute to the progression of cancer, according to a paper in the August 2011 issue of the journal Molecular and Cellular Biology. Silencing this particular gene ...

Lack of oxygen in cancer cells leads to growth and metastasis

September 13, 2012

(Medical Xpress)—It seems as if a tumor deprived of oxygen would shrink. However, numerous studies have shown that tumor hypoxia, in which portions of the tumor have significantly low oxygen concentrations, is in fact linked ...

Awakening genes that suppress tumors

October 10, 2013

(Medical Xpress)—When genes that normally suppress tumor growth are themselves suppressed, cancer cells can grow and proliferate uncontrollably. A new study led by a researcher at Yale University has uncovered the pathway ...

Recommended for you

Researchers thwart cancer cells by triggering 'virus alert'

August 27, 2015

Working with human cancer cell lines and mice, researchers at the Johns Hopkins Kimmel Cancer Center and elsewhere have found a way to trigger a type of immune system "virus alert" that may one day boost cancer patients' ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.