Master regulator of key cancer gene found, offers new drug target

June 25, 2014

A key cancer-causing gene, responsible for up to 20 percent of cancers, may have a weak spot in its armor, according to new research from the Masonic Cancer Center, University of Minnesota.

The partnership of MYC, a gene long linked to cancer, and a non-coding RNA, PVT1, could be the key to understanding how MYC fuels cancer cells. The research is published in the latest issue of the journal Nature.

"We knew MYC amplifications cause cancer. But we also know that MYC does not amplify alone. It often pairs with adjacent chromosomal regions. We wanted to know if the neighboring genes played a role," said lead author Anindya Bagchi, Ph.D., assistant professor in the University of Minnesota Medical School, the College of Biological Sciences and member of the Masonic Cancer Center. "We took a chance and were surprised to find this unexpected and counter-intuitive partnership between MYC and its neighbor, PVT1. Not only do these genes amplify together, PVT1 helps boost the MYC protein's ability to carry out its dangerous activities in the cell."

Contributors to this research include Yuen-Yi Tseng, graduate student with Anindya Bagchi, David Largaespada, Ph.D., professor in the College of Biological Sciences, Yasuhiko Kawakami, Ph.D., assistant professor in the College of Biological Sciences, York Marahrens, Ph.D., associate professor in the College of Biological Sciences and Kathryn Schwertfeger, Ph.D., assistant professor in the University of Minnesota's Medical School.

Bagchi and his team focused on a region of the genome, 8q24, which contains the MYC gene and is commonly expressed in cancer. The team separated MYC from the neighboring region containing the non-coding RNA PVT1. Using a specialized gene manipulation technique called chromosome engineering, researchers developed genetically engineered mouse strains in three separate iterations: MYC only, the rest of the region containing PVT1 but without MYC and the pairing of MYC with the regional genes.

The expected outcome, if MYC was the sole driver of the cancer, was tumor growth on the MYC line as well as the paired line. However, researchers found growth only on the paired line. This indicates MYC is not acting alone and needs help from adjacent genes.

"The discovery of this partnership gives us a stronger understanding of how MYC amplification is fueled. When cancer promotes a cell to make more MYC, it also increases the PVT1 in the cell, which in turn boosts the amount of MYC. It's a cycle, and now we've identified it, we can look for ways to uncouple this dangerous partnership," said Largaespada.

Testing this theory of uncoupling, researchers looked closely at several breast and colorectal cancers which are driven by MYC. For example, in colorectal cancer lab models, where a mutation in the beta-catenin gene drives MYC to cancerous levels, eliminating PVT1 from these cells made the tumors nearly disappear.

"Finding the cooperation between MYC and PVT1 could be a game changer. We used to think MYC amplification is the major issue, but ignored that other co-amplified genes, such as PVT1, can be significant," said Tseng, the paper's first author. "In this study, we show that PVT1 can be a key regulator of MYC protein, which can shift the paradigm in our understanding of MYC amplified cancers."

MYC has been notoriously elusive as a drug target. By uncoupling MYC and PVT1, researchers suspect they could disable the cancer growth and limit MYC to pre-cancerous levels. This would make PVT1 an ideal drug target to potentially control a major cancer gene.

"This is a thrilling discovery, but there are more questions that follow," said Bagchi. "Two major areas present themselves now for research: will breaking the nexus between MYC and PVT1 perform the same in any MYC-driven , even those not driven by this specific genetic location? And how is PVT1 stabilizing or boosting MYC within the cells? This relationship will be a key to developing any drugs to target this mechanism."

Explore further: New findings on neurogenesis in the spinal cord

Related Stories

New findings on neurogenesis in the spinal cord

March 5, 2014
Research from Karolinska Institutet in Sweden suggests that the expression of the so called MYC gene is important and necessary for neurogenesis in the spinal cord. The findings are being published in the journal EMBO Reports.

Survival protein a potential new target for many cancers

January 7, 2014
Walter and Eliza Hall Institute researchers have discovered a promising strategy for treating cancers that are caused by one of the most common cancer-causing changes in cells.

Researchers show Myc protein is cancer's 'volume control'

October 1, 2012
(Medical Xpress)—A protein called Myc, commonly found at high levels inside cancer cells, fuels the disease by allowing cells to override their in-built self-destruct mechanisms, according to two new studies by US scientists.

Major cancer protein amplifies global gene expression

September 27, 2012
Scientists may have discovered why a protein called MYC can provoke a variety of cancers. Like many proteins associated with cancer, MYC helps regulate cell growth. A study carried out by researchers at the National Institutes ...

Hard-to-treat Myc-driven cancers may be susceptible to drug already used in clinic

December 14, 2012
Drugs that are used in the clinic to treat some forms of breast and kidney cancer and that work by inhibiting the signaling molecule mTORC1 might have utility in treating some of the more than 15 percent of human cancers ...

Recommended for you

Physical activity could combat fatigue, cognitive decline in cancer survivors

July 25, 2017
A new study indicates that cancer patients and survivors have a ready weapon against fatigue and "chemo brain": a brisk walk.

Breaking the genetic resistance of lung cancer and melanoma

July 25, 2017
Researchers from Monash University and the Memorial Sloan Kettering Cancer Center (MSKCC, New York) have discovered why some cancers – particularly lung cancer and melanoma – are able to quickly develop deadly resistance ...

Anti-cancer chemotherapeutic agent inhibits glioblastoma growth and radiation resistance

July 24, 2017
Glioblastoma is a primary brain tumor with dismal survival rates, even after treatment with surgery, chemotherapy and radiation. A small subpopulation of tumor cells—glioma stem cells—is responsible for glioblastoma's ...

New therapeutic approach for difficult-to-treat subtype of ovarian cancer identified

July 24, 2017
A potential new therapeutic strategy for a difficult-to-treat form of ovarian cancer has been discovered by Wistar scientists. The findings were published online in Nature Cell Biology.

Immune cells the missing ingredient in new bladder cancer treatment

July 24, 2017
New research offers a possible explanation for why a new type of cancer treatment hasn't been working as expected against bladder cancer.

No dye: Cancer patients' gray hair darkened on immune drugs

July 21, 2017
Cancer patients' gray hair unexpectedly turned youthfully dark while taking novel drugs, and it has doctors scratching their heads.

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.