Cancer biologists link tumor suppressor gene to stem cells

March 26, 2014
UT Southwestern cancer biologists link tumor suppressor gene to stem cells
Dr. John Abrams, professor of cell biology (left), and Annika Wylie, a graduate student in genetics and development, discovered that an ancient gene called p53 activates stem cells when damage is present. Credit: UT Southwestern Medical Center

Just as archeologists try to decipher ancient tablets to discern their meaning, UT Southwestern Medical Center cancer biologists are working to decode the purpose of an ancient gene considered one of the most important in cancer research.

The p53 gene appears to be involved in signaling other cells instrumental in stopping tumor development. But the p53 gene predates cancer, so scientists are uncertain what its original function is.

In trying to unravel the mystery, Dr. John Abrams, Professor of Cell Biology at UT Southwestern, and his team made a crucial new discovery – tying the p53 gene to . Specifically, his lab found that when cellular damage is present, the gene is hyperactive in stem cells, but not in other cells. The findings suggest p53's tumor suppression ability may have evolved from its more ancient ability to regulate stem cell growth.

"The discovery was that only the stem cells light up. None of the others do. The exciting implication is that we are able to understand the function of p53 in stem cells," said Dr. Abrams, Chair of the Genetics and Development program in UT Southwestern's Graduate School of Biomedical Sciences. "We may, in fact, have some important answers for how p53 suppresses tumors."

The findings appear online in the journal eLife, a joint initiative of the Howard Hughes Medical Institute, the Max Planck Society, and the Wellcome Trust.

p53 is one of the hardest working and most effective allies in the fight against cancer, said Dr. Abrams. It regulates other genes, marshaling them to carry out an untold number of preemptive attacks and obliterate many pre-cancerous cells before they ever pose a threat. In nearly every case where there's a tumor, p53 is damaged or deranged, strongly suggesting that it is a tumor suppressant.

Stem cells are one of the body's most useful cells because of their regenerative capabilities. Stem cells produce , one that is a stem cell and another that can become virtually any kind of cell that's needed, such as a blood cell or a kidney cell. Stem cells have received tremendous attention in because of the stem cell hypothesis. That hypothesis maintains that malignant tumors are initiated and maintained by a population of that have properties similar to adult stem cells.

"What this new finding tells us is that an ancient functionality of p53 was hard-wired into stem cell function," said Dr. Abrams, senior author. "From the standpoint of trying to decipher cancer biology, that's a pretty profound observation."

To study the gene, researchers in Dr. Abrams lab, including Dr. Annika Wylie, postdoctoral research fellow and first author on the paper, developed a transgenic sensor that makes cells glow when they are active in Drosophila, or fruit flies. Other UT Southwestern researchers involved included Dr. Michael Buszczak, Assistant Professor of Molecular Biology.

Explore further: A gene family that suppresses prostate cancer

Related Stories

A gene family that suppresses prostate cancer

March 13, 2014
Cornell University researchers report they have discovered direct genetic evidence that a family of genes, called MicroRNA-34 (miR-34), are bona fide tumor suppressors.

p53 cuts off invading cancer cells

March 24, 2014
The tumor suppressor p53 does all it can to prevent oncogenes from transforming normal cells into tumor cells by killing defective cells or causing them to become inactive. Sometimes oncogenes manage to initiate tumor development ...

New study shows promise for preventing therapy resistance in tumor cells

January 9, 2014
A new study led by University of Kentucky researchers suggests that activating the tumor suppressor p53 in normal cells causes them to secrete Par-4, another potent tumor suppressor protein that induces cell death in cancer ...

Stem cell study finds source of earliest blood cells during development

March 21, 2014
Hematopoietic stem cells are now routinely used to treat patients with cancers and other disorders of the blood and immune systems, but researchers knew little about the progenitor cells that give rise to them during embryonic ...

Recommended for you

Anti-cancer chemotherapeutic agent inhibits glioblastoma growth and radiation resistance

July 24, 2017
Glioblastoma is a primary brain tumor with dismal survival rates, even after treatment with surgery, chemotherapy and radiation. A small subpopulation of tumor cells—glioma stem cells—is responsible for glioblastoma's ...

New therapeutic approach for difficult-to-treat subtype of ovarian cancer identified

July 24, 2017
A potential new therapeutic strategy for a difficult-to-treat form of ovarian cancer has been discovered by Wistar scientists. The findings were published online in Nature Cell Biology.

Immune cells the missing ingredient in new bladder cancer treatment

July 24, 2017
New research offers a possible explanation for why a new type of cancer treatment hasn't been working as expected against bladder cancer.

Shooting the achilles heel of nervous system cancers

July 20, 2017
Virtually all cancer treatments used today also damage normal cells, causing the toxic side effects associated with cancer treatment. A cooperative research team led by researchers at Dartmouth's Norris Cotton Cancer Center ...

Molecular changes with age in normal breast tissue are linked to cancer-related changes

July 20, 2017
Several known factors are associated with a higher risk of breast cancer including increasing age, being overweight after menopause, alcohol intake, and family history. However, the underlying biologic mechanisms through ...

Immune-cell numbers predict response to combination immunotherapy in melanoma

July 20, 2017
Whether a melanoma patient will better respond to a single immunotherapy drug or two in combination depends on the abundance of certain white blood cells within their tumors, according to a new study conducted by UC San Francisco ...

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.