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

Tracking how multiple myeloma evolves by sequencing DNA in the blood

December 10, 2017
Although people with multiple myeloma usually respond well to treatment, the blood cancer generally keeps coming back. Following genetic changes in how the disease evolves over time will help to understand the disease and, ...

Landmark CAR-T cancer study published

December 10, 2017
Loyola University Medical Center is the only Chicago center that participated in the pivotal clinical trial of a groundbreaking cancer treatment that genetically engineers a patient's immune system to attack cancer cells.

Study finds emojis promising tool for tracking cancer patients' quality of life

December 10, 2017
In findings presented to the American Society of Hematology, Mayo Clinic researchers found that using emojis instead of traditional emotional scales were helpful in assessing patients' physical, emotional and overall quality ...

Study explores use of checkpoint inhibitors after relapse from donor stem cell transplant

December 10, 2017
Immunotherapy agents known as checkpoint inhibitors have shown considerable promise in patients with hematologic cancers who relapse after a transplant with donor stem cells. Preliminary results from the first clinical trial ...

Blood test may help predict which breast cancers will recur

December 8, 2017
A blood test five years after breast cancer treatment helped identify some women who were more likely to relapse, long before a lump or other signs appeared, a preliminary study found.

Alcohol-abuse drug Antabuse kills cancer cells

December 8, 2017
A new study in Nature by an international team including researchers from Karolinska Institutet, reports that the alcohol-abuse drug Antabuse is effective against cancer. The study also identifies a potential mechanism of ...

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.