Study reveals how transcription factor EVI1 contributes to cancer development and tumor invasion

June 20, 2012
Credit: iStockphoto.com/AlexRaths

Since its discovery close to 25 years ago, the EVI1 gene has emerged as a major player in many different types of cancer, including leukemia and tumors of the breast, prostate and colon, among other organs. In the US, for example, there is a company called NanoOncology that was founded to develop drugs for blocking this oncogene. Yet, despite all the interest in EVI1, very few of the gene’s downstream targets are known.

Emilie Bard-Chapeau at the A*STAR Institute of Molecular and Cell Biology and co-workers1 have now used a systems biology approach to identify a slew of tumor-associated genes that are controlled by EVI1. The discovery could lead to new therapeutic strategies to combat various forms of cancer.

The EVI1 gene — short for ‘ecotropic viral integration site 1’ — encodes a zinc-finger transcription factor with two distinct DNA binding domains. When overexpressed, this leads to aggressive forms of cancer and poor patient survival. To better understand the biochemical functions of EVI1, Bard-Chapeau and co-workers searched for gene promoters and cooperating that are actively bound by EVI1 in human ovarian cancer and chronic myeloid cell lines.

Systems biology uses a palette of analytical and computational techniques to study the complex interactions in biological systems. Using microarrays, ChIP-sequencing and immunoprecipitation assays, the researchers found that the two different zinc-finger domains of EVI1 activate unique sets of target genes, many of which are involved in cell adhesion, proliferation, colony formation and other aspects of growth.

Notably, the researchers documented a strong association between EVI1 and FOS — the latter being one of the main components of the activator protein 1 (AP1) transcription factor complex that is known to drive tumorigenesis. Experiments in cell lines showed that EVI1 and FOS interact to co-regulate many hallmarks of cancer, and follow-up analyses in late-stage ovarian cancers taken from patients revealed an enrichment in expressed genes linked to both EVI1 and AP1. Taken together, the findings suggest that EVI1 expression might serve to fully elicit FOS oncogenic potential through a feed-forward regulatory loop that drives abnormal tissue changes.

“Our study has provided new mechanistic insights into the regulatory mechanism of EVI1, and revealed how EVI1 can function as a central player in many types of late-stage cancers,” says Bard-Chapeau. “Disruption of the interaction between EVI1 and FOS may be a very interesting way to prevent cancer progression.”

Explore further: New approach to link genome-wide association signals to biological function

More information: Bard-Chapeau, E. A. et al. Ecotopic viral integration site 1 (EVI1) regulates multiple cellular processes important for cancer and is a synergistic partner for FOS protein in invasive tumors. Proceedings of the National Academy of Sciences 109, 2168–2173 (2012).

Related Stories

New approach to link genome-wide association signals to biological function

June 30, 2011
Researchers have developed a new strategy to improve the outcome of genome-wide association (GWA) studies.

Scientists identify new mechanism of prostate cancer cell metabolism

March 22, 2012
Cancer cell metabolism may present a new target for therapy as scientists have uncovered a possible gene that leads to greater growth of prostate cancer cells.

New lung cancer gene found

July 19, 2011
A major challenge for cancer biologists is figuring out which among the hundreds of genetic mutations found in a cancer cell are most important for driving the cancer’s spread.

New study identifies novel role for PEA-15 protein in cancer growth

November 21, 2011
A new study from the University of Hawaii Cancer Center reveals that PEA-15, a protein previously shown to slow ovarian tumor growth and metastasis, can alternatively enhance tumor formation in kidney cells carrying a mutation ...

Recommended for you

Outdoor light at night linked with increased breast cancer risk in women

August 17, 2017
Women who live in areas with higher levels of outdoor light at night may be at higher risk for breast cancer than those living in areas with lower levels, according to a large long-term study from Harvard T.H. Chan School ...

Scientists develop novel immunotherapy technology for prostate cancer

August 17, 2017
A study led by scientists at The Wistar Institute describes a novel immunotherapeutic strategy for the treatment of cancer based on the use of synthetic DNA to directly encode protective antibodies against a cancer specific ...

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 ...

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 ...

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. ...

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.