Nav: Home

Study reveals amyloid clumps of a truncated p53 structure related to endometrial cancer

May 03, 2019

Brazilian scientists identify the predominant presence of a truncated variant of the p53 protein in amyloid aggregates in endometrial cancer cells. Such structures are related to the progression of this tumor.

A finding by Brazilian researchers promises new perspectives for the treatment of Type 2 endometrial cancer, the most aggressive form of one of the most frequent gynecological tumors. Using in-vitro tests, they identified a high accumulation of aggregates formed by a truncated variant of p53 protein, termed Δ40p53. The variant was found in the cytoplasm of cancer cells. This is the first time that scientists have observed variants of p53 forming amyloid aggregates in tumor cells (similar to that found with mutant whole p53).

The study was conducted by professors Etel Gimba from the Fluminense Federal University and the National Cancer Institute, and Jerson Lima Silva, from the Federal University of Rio de Janeiro. The results were published in the Journal of Biological Chemistry.

Called the guardian of the human genome, p53 is a protein that normally inhibits the onset and growth of tumors by regulating the cell cycle and protecting DNA. Mutations in the genes coding for this protein, however, may promote loss of function and gain of a new behavior, detrimental to the cell. These genetic changes occur in more than half of cancer cases worldwide, and one of the consequences is the formation of p53 amyloid aggregates, resulting in the unbridled growth of tumor cells.

However, not all tumors have mutations in the p53 gene. In some cases, they present alterations in other cellular and genetic mechanisms related to this protein, such as its location in the cell or the abnormal presence of its truncated isoforms. These variants of the protein have been known for at least 14 years, but scientists didn't know whether they contributed to the formation of p53 protein aggregates. This is the phenomenon the Brazilians set out to study.

The researchers observed that, in the case of endometrial cancer, the Δ40p53 isoform plays the predominant role, presenting higher aggregation properties than the full p53 in the cancer cells. The novelty in this recent work is the higher propensity of the truncated form to assemble into the amyloid clumps, especially in the cytoplasm, in contrast to mutant full-length p53 that tends to aggregate in the nucleus. "This shows that these variants can modulate the aggregation state of p53", explains Etel Gimba.

Based on these results it should be possible to find compounds capable of inhibiting the formation of these aggregates through a specific action on the truncated variants. "One of the major difficulties [in cancer treatment] is being able to undo these aggregates as a therapeutic strategy", says Etel Gimba. "By specifically undoing the aggregates formed by these variants, we increase the chances of reversing their misfolded, aggregated state, opening the door for the body to discard the aberrant cells", adds the researcher.

This may represent a revolution in the treatment of endometrial cancer, since changes in p53 are associated with Type 2 of the disease, with a high mortality rate. It is crucial for the prognostic evaluation of endometrial tumors. "Patients who have alterations in the p53 pathway since the beginning of the development of the tumors will present very aggressive tumors, difficult to treat", highlights the research coordinator.

The tests were done in vitro, with the use of immunofluorescence, light-scattering kinetics, circular dichroism and transmission electron microscopy.
The article entitled "Loss of the p53 transactivation domain results in high amyloid aggregation of the Δ40p53 isoform in endometrial carcinoma cells" can be read in the Journal of Biological Chemistry.

Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem (INBEB)

Related Cancer Cells Articles:

Drug that keeps surface receptors on cancer cells makes them more visible to immune cells
A drug that is already clinically available for the treatment of nausea and psychosis, called prochlorperazine (PCZ), inhibits the internalization of receptors on the surface of tumor cells, thereby increasing the ability of anticancer antibodies to bind to the receptors and mount more effective immune responses.
Engineered bone marrow cells slow growth of prostate and pancreatic cancer cells
In experiments with mice, researchers at the Johns Hopkins Kimmel Cancer Center say they have slowed the growth of transplanted human prostate and pancreatic cancer cells by introducing bone marrow cells with a specific gene deletion to induce a novel immune response.
First phase i clinical trial of CRISPR-edited cells for cancer shows cells safe and durable
Following the first US test of CRISPR gene editing in patients with advanced cancer, researchers report these patients experienced no negative side effects and that the engineered T cells persisted in their bodies -- for months.
Zika virus' key into brain cells ID'd, leveraged to block infection and kill cancer cells
Two different UC San Diego research teams identified the same molecule -- αvβ5 integrin -- as Zika virus' key to brain cell entry.
Plant-derived SVC112 hits cancer stem cells, leaves healthy cells alone
Study shows Colorado drug SVC112 stops production of proteins that cancer stem cells need to survive and grow.
Changes in the metabolism of normal cells promotes the metastasis of ovarian cancer cells
A systematic examination of the tumor and the tissue surrounding it -- particularly normal cells in that tissue, called fibroblasts -- has revealed a new treatment target that could potentially prevent the rapid dissemination and poor prognosis associated with high-grade serous carcinoma (HGSC), a tumor type that primarily originates in the fallopian tubes or ovaries and spreads throughout the abdominal cavity.
The development of brain stem cells into new nerve cells and why this can lead to cancer
Stem cells are true Jacks-of-all-trades of our bodies, as they can turn into the many different cell types of all organs.
White blood cells related to allergies may also be harnessed to destroy cancer cells
A new Tel Aviv University study finds that white blood cells which are responsible for chronic asthma and modern allergies may be used to eliminate malignant colon cancer cells.
Conversion of breast cancer cells into fat cells impedes the formation of metastases
An innovative combination therapy can force malignant breast cancer cells to turn into fat cells.
Breast cancer cells in mice tricked into turning into fat cells
As cancer cells respond to cues in their microenvironment, they can enter a highly plastic state in which they are susceptible to transdifferentiation into a different type of cell.
More Cancer Cells News and Cancer Cells Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Teaching For Better Humans 2.0
More than test scores or good grades–what do kids need for the future? This hour, TED speakers explore how to help children grow into better humans, both during and after this time of crisis. Guests include educators Richard Culatta and Liz Kleinrock, psychologist Thomas Curran, and writer Jacqueline Woodson.
Now Playing: Science for the People

#556 The Power of Friendship
It's 2020 and times are tough. Maybe some of us are learning about social distancing the hard way. Maybe we just are all a little anxious. No matter what, we could probably use a friend. But what is a friend, exactly? And why do we need them so much? This week host Bethany Brookshire speaks with Lydia Denworth, author of the new book "Friendship: The Evolution, Biology, and Extraordinary Power of Life's Fundamental Bond". This episode is hosted by Bethany Brookshire, science writer from Science News.
Now Playing: Radiolab

One of the most consistent questions we get at the show is from parents who want to know which episodes are kid-friendly and which aren't. So today, we're releasing a separate feed, Radiolab for Kids. To kick it off, we're rerunning an all-time favorite episode: Space. In the 60's, space exploration was an American obsession. This hour, we chart the path from romance to increasing cynicism. We begin with Ann Druyan, widow of Carl Sagan, with a story about the Voyager expedition, true love, and a golden record that travels through space. And astrophysicist Neil de Grasse Tyson explains the Coepernican Principle, and just how insignificant we are. Support Radiolab today at