A tiny piece of a protein could be key to keep breast cancer from growing.
A discovery at the University of Central Florida College of Medicine may in the future help detect cancer cells in patients before these cells have a chance to metastasize or spread through the body.
Annette Khaled, a UCF professor and cancer researcher who has spent the last eight years studying ways to inhibit breast cancer metastases, published her lab’s results in last month’s Scientific Reports.
Khaled leads the medical school’s cancer research division and is looking at how and why cells escape the primary cancer tumor and then spread to organs like the lungs, brain and bones, where they cause 90 percent of cancer deaths.
Supported with funding from the National Institutes of Health (NIH) and the Breast Cancer Research Foundation, she previously was able to show that a molecular complex called a chaperonin (or CCT for short) — which helps proteins to fold into functional units — is especially active in cancer cells.
Her team developed a peptide to blocks the folding mechanism and placed it in a nanoparticle to deliver straight to cancer cells. Without the ability to have their proteins fold, the cancer cells died.
Khaled knew her nanoparticle was disabling the folding system but didn’t know how. Complicating that understanding was the fact that the CCT complex is a giant cellular machine and made up of eight different subunits.
In her latest study, Khaled discovered how the cancer killing happened.
She discovered that one of the subunits — “Subunit 2” — is the leader that makes the whole cellular system work.
“Adding Subunit 2 can make normal cells act like cancer cells,” she says. “Subunit 2 leads and the others follow.”
Defining Subunit 2’s role took months of study. The UCF scientist discovered that adding more Subunit 2 caused cancer cells to grow and move. Depleting the subunit caused cancer cells to ultimately die.
“Understanding cancer is like trying to solve a giant jigsaw puzzle,” Khaled explains. “And with this discovery, we feel like we’ve found some of the parts that make up the puzzle’s edge. We all have a little Subunit 2 in our cells and our levels go up and down based on demands for protein-folding. But in cancer cells that need to grow and invade, Subunit 2 seems to be on all the time.
“Based on our new research, we can work to discover markers that identify cancer cells in which Subunit 2 is increasing, making these cells susceptible to our nanomedicine.”
The next phase of Khaled’s Subunit 2 research was advanced by gifts from the Catherine McCaw-Engelman and Family Cancer Research Collaborative and the Hardee Family Foundation. Based on her latest findings in Scientific Reports, Khaled is next turning to detecting circulating cancer cells in blood with high levels of Subunit 2. Such testing could give physicians another indicator of whether the patient’s cancer is spreading.
“What I want to do is get these guys,” Khaled says of her work to stop spreading cancer cells. “With this study, we are one step closer.”
