'Jumonji' protein key to Ewing's sarcoma rampage

March 24, 2017, CU Anschutz Medical Campus
Sechler and colleagues show gene KDM3A may be essential to Ewing's Sarcoma spread. Credit: University of Colorado Cancer Center

By the time Ewing's Sarcoma is diagnosed, primarily in teens and young adults, it has often spread from its primary site to other parts of the body, making it difficult to treat. A University of Colorado Cancer Center study published in the journal Oncogene pinpoints a protein that may be essential to this spread - when researchers knocked down the protein KDM3A in Ewing's Sarcoma tumor cells, one of a family known as Jumonji proteins, they also inhibited the cancer's metastatic ability.

"A cell has to be able to move in order to infiltrate new tissues. We show that KDM3A is an important part of this cell motility," says lead author Marybeth Sechler, graduate student in the lab of CU Cancer Center investigator Paul Jedlicka, MD, PhD.

The Jedlicka lab had previously identified KDM3A as a tumor promoter in Ewing's Sarcoma, and the current study extends this work to show the protein's role in the 's ability to metastasize. Specifically, the group used global gene expression profiling to show that the presence of KDM3A up-regulates pathways known to be involved in migration and metastasis.

Additionally, the group looked downstream from KDM3A to show that another known as Melanoma Cell Adhesion Molecule (MCAM) may be another essential link in the chain of events that leads to metastasis. When the group knocked down MCAM, it had a similar effect against metastasis as knocking down KDM3A. And when MCAM was left intact, cancer were able to use this MCAM to partially avoid the effects of KDM3A knockdown.

"We were looking for potential candidates to target in the of Ewing's Sarcoma that might be druggable, and now we have two," Sechler says.

As a whole, the family of Jumonji proteins is involved in histone demethylation - a mechanism that affects gene accessibility and expression. Sechler says the family is an especially attractive target for cancer therapeutics because, "one demethylase can affect a larger group of genes. If we can find functions that promote or act against cancer, we could affect whole gene programs."

Previous work has shown that pan-Jumonji inhibitors - those drugs that silence the function of the entire family - may act against cancer without necessarily acting against healthy cells.

"You can treat non- with it and they seem to do okay," Sechler says.

The lab's next steps are to evaluate the use of Jumonji inhibitors against Ewing's Sarcoma, while also further unpacking the mechanics of MCAM.

"We want to know what pathways it's feeding into and how, in turn, these pathways are promoting the cancer," Sechler says. "This could be an important step toward identifying better targets for treating this disease."

Explore further: Possible new druggable target in Ewing's Sarcoma

More information: M Sechler et al, The histone demethylase KDM3A, and its downstream target MCAM, promote Ewing Sarcoma cell migration and metastasis, Oncogene (2017). DOI: 10.1038/onc.2017.44

Related Stories

Possible new druggable target in Ewing's Sarcoma

January 22, 2014
Ewing's Sarcoma is an aggressive pediatric cancer, most commonly caused by the improper fusion of the gene EWS with the gene FLI1. Though the cause has long been known, therapeutic targeting of this fusion has to date proven ...

New potential therapeutic strategy against a very aggressive infant bone cancer

January 29, 2015
Researchers at the Bellvitge Biomedical Research Institute (IDIBELL), led by Oscar Martínez Tirado participated in an international study which suggests inhibition of Sirtuin1 (SIRT1) protein as a future treatment option ...

A noncoding RNA promotes pediatric bone cancer

November 17, 2014
Ewing sarcoma is a cancer of bone or its surrounding soft tissue that primarily affects children and young adults. A hallmark of Ewing sarcoma is a translocation event that results in the fusion of an RNA binding protein, ...

Serendipity leads to discovery of adult cancer genes in young-adult Ewing Sarcoma

February 3, 2015
A University of Colorado Cancer Center study published in the journal PLoS One finds alterations in expression of genes PIK3R3 and PTEN, more commonly observed in adult tumors, in the rare, young-adult bone cancer Ewing Sarcoma, ...

Epigenetic diversity in childhood cancer

January 30, 2017
Tumors of the elderly, such as breast cancer and colon cancer, accumulate thousands of DNA mutations. These genetic defects contribute to cancer-specific properties including uncontrolled growth, invasion in neighboring tissues, ...

New marker, new target in Ewing's sarcoma

June 30, 2012
Ewing's sarcoma is a bone cancer commonly diagnosed in about 250 U.S. teenagers per year. If early chemotherapy is effective, improvement can be durable. But for children and teens who respond poorly to a first attempt at ...

Recommended for you

Standard chemotherapy treatment for HPV-positive throat cancer remains the most effective, study finds

November 15, 2018
A new study funded by Cancer Research UK and led by the University of Birmingham has found that the standard chemotherapy used to treat a specific type of throat cancer remains the most effective.

New 'SLICE' tool can massively expand immune system's cancer-fighting repertoire

November 15, 2018
Immunotherapy can cure some cancers that until fairly recently were considered fatal. In addition to developing drugs that boost the immune system's cancer-fighting abilities, scientists are becoming expert at manipulating ...

Anti-malaria drugs have shown promise in treating cancer, and now researchers know why

November 15, 2018
Anti-malaria drugs known as chloroquines have been repurposed to treat cancer for decades, but until now no one knew exactly what the chloroquines were targeting when they attack a tumor. Now, researchers from the Abramson ...

Researchers identify a mechanism that fuels cancer cells' growth

November 14, 2018
Scientists at the UCLA Jonsson Comprehensive Cancer Center have identified sodium glucose transporter 2, or SGLT2, as a mechanism that lung cancer cells can utilize to obtain glucose, which is key to their survival and promotes ...

A new approach to detecting cancer earlier from blood tests: study

November 14, 2018
Cancer scientists led by principal investigator Dr. Daniel De Carvalho at Princess Margaret Cancer Centre have combined "liquid biopsy", epigenetic alterations and machine learning to develop a blood test to detect and classify ...

New antibody breakthrough to lead the fight against cancer

November 14, 2018
Scientists at the University of Southampton have developed a new antibody that could hold the key to unlocking cancer's defence against the body's immune system.


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.