Researchers Study Cancer Treatment Recovery Mechanism

A previously overlooked protein, beta-catenin, may counteract both medical and accidental radiation exposure.

UCSD School of Medicine researchers discovered that beta-catenin, a previously overlooked protein, plays a crucial role in promoting hematopoietic stem cell recovery after cancer treatments. These findings were published in the May 1 issue of the Genes and Development journal. 

Traditional cancer remedies usually involve large chemotherapy and radiation doses, both of which can be fatal due to accidental destruction of exposed hematopoietic stem cells — bone marrow cells that produce blood cells. To counter this, patients are usually given replacement transplants to help replenish their blood stores, although success is not always guaranteed. 

UCSD pharmacology professor Dr. Tannishtha Reya and colleagues from several institutions used mouse models at Duke University to further study radiation’s effects on these stem cells. They observed that radiation exposure triggers a critical cellular signaling pathway called Wnt in hematopoietic stem and progenitor cells, thanks to the body’s self-monitoring mechanisms that detect when tissues are damaged.

“The Wnt pathway and its key mediator, beta-catenin, are critical for embryonic development and establishment of the body plan,” Reya said in an April 30 UCSD News Center release. “In addition, the Wnt pathway is activated in stem cells from many tissues and is needed for their continued maintenance.”

According to Reya, lower organisms often use the Wnt pathway for regenerative purposes. The team tested this pathway to see if it could be utilized in human clinical treatments. In their models, the researchers found that the mice, which were made deficient in the beta-catenin protein, could not activate the Wnt pathway, leading to poor bone marrow recovery from radiation therapy.

The study confirmed that the Wnt pathway can significantly increase its activity after sensing radiation damage, therefore increasing the rate that destroyed stem cells are replaced. The team now looks toward ways of applying the discovery in real-life scenarios.

“Our work shows that Wnt signaling is important in the mammalian hematopoietic system and is critical for recovery from chemotherapy and radiation,” Reya said to the News Center. “While these therapies can be lifesaving, they take a heavy toll on the hematopoietic system from which the patient may not always recover.”

She added that the research could have implications for improving cancer cures because the risk of collateral damage to normal tissue limits radiation’s effectiveness, and even patients that successfully undergo treatment may not recuperate in time to fight off secondary infections or anemia. The work on beta-catenin contributed to a larger project focused on developing countermeasures to both medical and accidental radiation exposure.

“Understanding how the body regenerates normally might allow us to devise ways to enhance recovery in times of need, and that was the driving rationale for our work,” Reya told the UCSD Guardian. 

Future research will help create effective methods to mimic or accelerate the positive effects of the Wnt signaling pathway and its beta-catenin proteins in patients.