A maestro that conducts the invasiveness of glioblastoma tumors

June 14, 2018, Instituto Gulbenkian de Ciencia
ZEB1 is able to simultaneously switch 'on' and 'of' a large number of genes in cancer cells, in this way functioning as a 'conductor' that coordinates a genetic program that drives cell invasiveness of glioblastoma tumors. Credit: Visual Science Communication

Glioblastoma is the most severe form of brain cancer in adults. The aggressiveness of this cancer is largely due to its ability to invade surrounding brain tissue, making the tumor difficult to remove by surgery. Now, a research team led by Diogo Castro, from Instituto Gulbenkian de Ciencia (IGC, Portugal), has discovered a genetic programme that controls the invasiveness of this form of cancer. This research, published in The EMBO Journal, may open avenues for developing new therapies.

Glioblastoma is a tumor that often reappears after surgery. This is in part because its easily blend in with normal cells, making it difficult for the surgeon to remove the tumor in its entirety. Moreover, contains cancer stem cells with the capacity to originate a new tumor. If a few of these cells are left behind, a new tumor begins to form.

"The invasiveness of this form of tumor is a serious issue, and many researchers are trying to understand the mechanisms that allow to invade the surrounding brain tissue," says Diogo Castro. A molecule previously known to be involved in glioblastoma invasiveness is Zeb1. "Zeb1 belongs to an important group of regulatory molecules called transcription factors. These act inside the cell as a conductor does with an orchestra, telling musicians who should be playing, and when. Transcription factors do the same thing with genes," explained Pedro Rosmaninho, first author of this study.

"Our work confirmed the important role Zeb1 has in glioblastoma, by helping us to understand how it operates inside cancer cells when it enables them to invade the healthy around the tumor," added the IGC researcher. Using cultures of cells established from human biopsies, and genetic databases constructed from the analysis of hundreds of gliobastoma tumors, the research team mapped which genes within the genome are targeted by Zeb1. Strikingly, researchers observed that Zeb1 orchestrates changes in the properties of cancer cells, by playing a dual role: it is able to simultaneously switch "on" and "off" a vast number of genes. This changes how interact with each other, and makes them motile so they can migrate away from the tumor mass.

"The more we know about how glioblastoma cells invade the surrounding tissues, the closer we will be to one day finding effective therapies that disrupt this process," said Diogo Castro.

The estimated prevalence of glioblastoma in the population is one in every 100,000 inhabitants in Europe.

Explore further: Identification of PTPRZ as a drug target for cancer stem cells in glioblastoma

More information: Pedro Rosmaninho et al, Zeb1 potentiates genome‐wide gene transcription with Lef1 to promote glioblastoma cell invasion, The EMBO Journal (2018). DOI: 10.15252/embj.201797115

Related Stories

Identification of PTPRZ as a drug target for cancer stem cells in glioblastoma

July 19, 2017
Glioblastoma is a malignant brain tumor with high mortality. Cancer stem cells are thought to be crucial for tumor initiation and its recurrence after standard therapy with radiation and temozolomide (TMZ) chemotherapy. Protein ...

Insights into how brain cancer evades the immune system

March 7, 2018
Glioblastoma—a universally fatal form of brain cancer—is known for its ability to hijack immune checkpoints and evade detection and destruction by the body's immune defenses. But many of the details underlying this feat ...

Researchers identify potential therapeutic target for deadly brain cancer

April 8, 2014
Researchers from the Geisel School of Medicine at Dartmouth will present a scientific poster on Tuesday, April 8, 2014 at the American Association of Cancer Researchers conference in San Diego, CA. The research identifies ...

Researchers create a promising new treatment for the deadliest form of brain cancer

September 2, 2015
UCLA scientists have developed a potentially promising new combination therapy for glioblastoma, the most common and deadliest form of brain cancer.

Using a microRNA to shift the makeup of glioblastoma subtypes

July 13, 2017
Glioblastoma multiforme (GBM), an extremely aggressive brain cancer, is a very complex disease. It is characterized by a fast-growing tumor in the brain composed of many subpopulations of cells, including glioblastoma stem ...

Researchers find new driver of an aggressive form of brain cancer

November 15, 2016
University of Hawai'i Cancer Center researchers have identified an essential driver of tumor cell invasion in glioblastoma, the most aggressive form of brain cancer that can occur at any age. The discovery can help researchers ...

Recommended for you

Dying cancer cells make remaining glioblastoma cells more aggressive and therapy-resistant

June 21, 2018
A surprising form of cell-to-cell communication in glioblastoma promotes global changes in recipient cells, including aggressiveness, motility, and resistance to radiation or chemotherapy.

Existing treatment could be used for common 'untreatable' form of lung cancer

June 21, 2018
A cancer treatment already approved for use in certain types of cancer has been found to block cell growth in a common form of lung cancer for which there is currently no specific treatment available.

Novel therapy makes oxidative stress deadly to cancer

June 21, 2018
Oxidative stress can help tumors thrive, but one way novel cancer treatments work is by pushing levels to the point where it instead helps them die, scientists report.

Higher body fat linked to lower breast cancer risk in younger women

June 21, 2018
While obesity has been shown to increase breast cancer risk in postmenopausal women, a large-scale study co-led by a University of North Carolina Lineberger Comprehensive Cancer Center researcher found the opposite is true ...

Researchers uncover new target to stop cancer growth

June 21, 2018
Researchers at the University of Wisconsin-Madison have discovered that a protein called Munc13-4 helps cancer cells secrete large numbers of exosomes—tiny, membrane-bound packages containing proteins and RNAs that stimulate ...

New treatment helps avoid deafness in child chemotherapy patients

June 21, 2018
An international trial has found that a medicine commonly used to treat poisoning is effective in reducing deafness in children receiving chemotherapy for cancer.

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.