Aging Tumor Cells May Provide Effective Treatment for Cancer

Could aging tumor cells provide an effective treatment for cancer? They just may be able to. Scientists have discovered that diffuse large B-cell lymphoma (DLBCL) may be susceptible to treatment by re-activating the normal aging program in tumor cells so that they can no longer divide.

Diffuse large B-cell lymphoma is the most common form of non-Hodgkin's lymphoma. In fact, it's estimated that 70,000 people living in the United States will be diagnosed with non-Hodgkins lymphoma in 2013. Roughly 50 percent of those diagnosed will not respond to conventional treatment or will relapse within five years.

The new study actually details a novel, tumor-suppressive role for the Smurf2 protein, which typically plays an "enforcer" role in cellular aging, also called senescence, in a subset of DLBCL. In 2012, the researchers noted that mice deficient in Smurf2 gene expression developed spontaneous tumors. That's why the scientists decided to take a closer look at Smurf2 expression in patients with DBLCL.

In the end, the researchers found that Smurf2 is part of a complex pathway incorporating the transcriptional regulator YY1 and the regulatory gene c-Myc (also a well-known oncogene). Together, these three proteins collaborate to regulate cell proliferation and division. However, in a subset of DLBCL patients this cycle has gone awry.

Tumor cells that showed decreased levels of Smurf2 expression also had increased levels of YY1 and c-Myc expression. These increased levels of YY1 and c-Myc caused cells to continue dividing, a hallmark of many cancers. The lack of Smurf2 also allowed the tumor cells to continue dividing longer.

"This enhanced cell proliferation induced by YYI and c-Myc activation, coupled with impaired senescence due to low Smurf2 levels helps drive lymphoma formation," said Hong Zhang, one of the researchers, in a news release. "It also suggests multiple roles for Smurf2 in tumor suppression in the form of suppressed cell proliferation and senescence response."

The findings reveal a little bit more about the role of Smurf2 in cancers. Currently, the scientists plan to screen for molecules that can either increase or mimic the expression of Smurf2. This, in turn, could provide an effective treatment for cancer.

The findings are published in the journal Nature Communications.