Team discovers mechanism responsible for tumor invasion in brain cancer

April 9, 2015
Investigators Discover Mechanism Responsible for Tumor Invasion in Brain Cancer
Invasion assays using Glioblastoma (GBM) cells on the left lacking Id4, in comparison to the same cells being genetically engineered to express Id4 on the right. Every invaded cell in this assay is colored green and the assay showed that the cells on the left, lacking Id4, invaded much more than the cells on the right in which there was forced expression of Id4.

A neuro-oncology research team at Dartmouth's Norris Cotton Cancer Center, led by the Director Mark A. Israel, MD with first author Gilbert J. Rahme, PhD, recently identified the transcription factor Id4 as a suppressor of tumor cell invasion in glioblastoma. Their paper, "Id4 suppresses MMP2-mediated invasion of glioblastoma-derived cells by direct inactivation of Twist1 function," was recently published in Oncogene. A key finding was the mechanism by which Id4 silences matrix metalloproteinase 2 (MMP2), determined to be inhibition of the protein Twist1 that is required for MMP2 expression.

"This finding suggests a novel therapeutic target to decrease invasion of in patients and may also provide a novel biomarker that could help predict survival of patients with glioblastoma," explained Israel.

Glioblastoma is the most lethal form of and leads to death in patients by invading the brain tissue in a process that allows single cells to move through normal brain tissue, which makes complete surgical removal of the tumor impossible. Israel and his team sought to understand the mechanisms that drive tumor invasion of normal tissue in glioblastoma.

Using data from The Cancer Genome Atlas (TCGA), the Dartmouth team demonstrated that Id4 expression correlates with survival of glioblastoma patients and inversely correlates with MMP2 expression. The data suggests that the upregulation of MMP2 resulting from decreased Id4 expression in multiforme (GBM) may contribute to the morbidity and mortality of GBM patients.

This study used Dartmouth's Shared Resources including Microscopy and Molecular Biology. "Using the core facilities greatly facilitated the conduct of the work saving time and reducing cost," Rahme said. All 14 of Dartmouth's Shared Resources are available to outside investigators by arrangement.

"Conventional drugs targeting the enzymes encoded by MMP genes have not been successful in the clinic due to adverse side effects," said Rahme. "We believe that proteins in the pathway that controls the expression of MMP2 are likely to be better therapeutic targets. Targeting Twist1 might silence MMP2 and decrease tumor invasion, which will help patients with GBM. Furthermore, the of Id4 may serve as a tumor biomarker that can predict the degree of tumor infiltration."

Looking forward, the therapeutic targets revealed in this study to be actors in tumor invasion need to be further characterized as drug targets and, if possible, therapeutically inhibited. Their pursuit of Id4 as a biomarker for with GBM continues in hopes of making useful predictions of and survival.

Explore further: Metabolic compensation underlies drug resistance in glioblastoma

Related Stories

Metabolic compensation underlies drug resistance in glioblastoma

March 23, 2015
Gliobststoma (GBM) is a highly aggressive brain tumor that is resistant to many conventional cancer therapies. The kinase mTOR induces pathways that are aberrantly activated in GBM. However, mTOR inhibitors have not shown ...

Researchers identify protein pathway involved in brain tumor stem cell growth

February 26, 2015
Glioblastomas are a highly aggressive type of brain tumor, with few effective treatment options. Moffitt Cancer Center researchers are one step closer to understanding glioblastoma development following the identification ...

Study identifies possible new target for future brain cancer drugs

February 27, 2014
A molecule in cells that shuts down the expression of genes might be a promising target for new drugs designed to treat the most frequent and lethal form of brain cancer, according to a new study by researchers at The Ohio ...

Glioblastoma: Study ties three genes to radiation resistance in recurrent tumors

February 3, 2015
A new study identifies three genes that together enable a lethal form of brain cancer to recur and progress after radiation therapy.

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 ...

Cancer genes deactivated in deadly brain cancer

April 3, 2015
Northwestern Medicine scientists have identified a small RNA molecule called miR-182 that can suppress cancer-causing genes in mice with glioblastoma mulitforme (GBM), a deadly and incurable type of brain tumor.

Recommended for you

Scientists develop blood test that spots tumor-derived DNA in people with early-stage cancers

August 16, 2017
In a bid to detect cancers early and in a noninvasive way, scientists at the Johns Hopkins Kimmel Cancer Center report they have developed a test that spots tiny amounts of cancer-specific DNA in blood and have used it to ...

Toxic formaldehyde is produced inside our own cells, scientists discover

August 16, 2017
New research has revealed that some of the toxin formaldehyde in our bodies does not come from our environment - it is a by-product of an essential reaction inside our own cells. This could provide new targets for developing ...

Cell cycle-blocking drugs can shrink tumors by enlisting immune system in attack on cancer

August 16, 2017
In the brief time that drugs known as CDK4/6 inhibitors have been approved for the treatment of metastatic breast cancer, doctors have made a startling observation: in certain patients, the drugs—designed to halt cancer ...

Popular immunotherapy target turns out to have a surprising buddy

August 16, 2017
The majority of current cancer immunotherapies focus on PD-L1. This well studied protein turns out to be controlled by a partner, CMTM6, a previously unexplored molecule that is now suddenly also a potential therapeutic target. ...

Researchers find 'switch' that turns on immune cells' tumor-killing ability

August 16, 2017
Molecular biologists led by Leonid Pobezinsky and his wife and research collaborator Elena Pobezinskaya at the University of Massachusetts Amherst have published results that for the first time show how a microRNA molecule ...

A metabolic treatment for pancreatic cancer?

August 15, 2017
Pancreatic cancer is now the third leading cause of cancer mortality. Its incidence is increasing in parallel with the population increase in obesity, and its five-year survival rate still hovers at just 8 to 9 percent. Research ...

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.