Exactly how do proteins help cancer cells survive?
Despite advances in research, this remains a mystery – and solving it could lead to new treatments that interfere with or block these proteins.
Recent research, conducted by UNC Chapel Hill’s Department of Biochemistry and Biophysics, may help.
In a study funded by the National Institutes of Health and published in September in the journal Oncogene, Tina Leisner and Leslie Parise show that one specific protein, CIB1, helps cancer cells survive.
“We had hints that interfering with this protein might slow cancer’s growth,” Leisner said. “When we found that loss of the protein was causing cancer cells to die, we were very excited.”
To study the effects of the protein, the team used a technique called RNA interference – RNAi. This technique allows researchers to prevent a cell from producing proteins such as CIB1, and reduces the level of proteins in a given cell by 90 percent or more.
Leisner and colleagues used RNAi to lower the levels of the CIB1 protein in breast cancer cells, as well as cells from neuroblastoma (a deadly form of childhood cancer). They found that reducing levels of the protein shut down two important cell “survival pathways.” These pathways, in which proteins such as CIB1 activate other molecules, signal a cell to continue living when it would otherwise die.
“Healthy cells do have these survival pathways, and the pathways are essential for normal cell function,” Leisner said. “Healthy cells activate them in a controlled and precise manner to maintain proper cell function.
“In tumor cells, however, the survival pathways are often hyper- or persistently activated, which allows tumor cells to evade cell death and grow unchecked.”
If CIB1 allows cancer cells to use “survival pathways,” then treatments that interfere with or block CIB1 could kill the cells and prevent the spread of the cancer.
Additionally, Leisner said, any treatment that interfered with CIB1 in healthy cells would not cause the healthy cells to die, meaning the treatments would have few side effects from the death of healthy tissue.
“Our preliminary data suggests that knocking out the CIB1 protein in normal healthy cells has no adverse effects.”
Leisner, along with her team from Leslie Parise’s lab, intends to further study the CIB1 protein in different types of cancer, as well as how drugs could target the protein.
“Other than short peptides, there are no compounds or small molecules that target CIB1,” Leisner said. “We see this as a promising drug target, and our research is moving in that direction.”