May lead to new approach to destroying cancer tumors.
Dying cells ensure that they will be replaced, and now a study has shown for the first time how they do it – a discovery that also suggests an ingenious new approach to shrinking cancerous tumors. A research team from Rush University Medical Center published a paper in the June 19 issue of the journal Developmental Cell describing these two groundbreaking discoveries.

“I believe this discovery is going to have important ramifications for cancer biology and cancer drug development, and for the treatment of other diseases, such as diabetic foot ulcers,” said Sasha Shafikhani, PhD, associate professor in the Department of Internal Medicine at Rush Medical College, who headed the study.

The team made its two–pronged discovery while investigating how an opportunistic microbe kills cancer cells. For years, Shafikhani’s lab has been studying Pseudomonas aeruginosa, a bacterium that can be lethal, but only to people who are already wounded or sick.

This pathogenic bacterium secretes several toxins that allow it to cause infection. One such toxin, ExoT, inhibits cell division and can severely impede wound healing, but it's also known to kill cancer cells.

The researchers were trying to figure out ExoT's lethal mechanisms against cancer when they unlocked, almost by accident, a mystery researchers have been trying to solve for decades. Before cells die, they alert their neighbors of the need to replace them and compensate for their demise, ensuring the organism’s survival. Medical researchers have been wondering for at least 20 years how cells manage to do it.

While shining a light on the lethal habits of Pseudomonas aeruginosa, Shafikhani’s team discovered what actually happens in that process, called compensatory proliferation signaling (CPS). The investigators saw – and have shown in amazing videos they produced – that during CPS, dying cells release microvesicles (a type of sac) containing the protein CrkI. These microvesicles travel to neighboring cells and upon contact cause them to create new cells to replace the ones that are dying.

In addition, Shafikhani and his colleagues demonstrated that when they knocked out the CrkI protein during CPS, either genetically or with the ExoT toxin, they could stop cell compensatory proliferation cold. That’s a trick Pseudomonas aeruginosa uses to take advantage of damaged tissues, but it has exciting possibilities for disease treatment as well.