A pathway called  "Unfolded Protein Response," or UPR, a cell's way of responding to unfolded and misfolded proteins, and helps tumour cells escape programmed cell death during the development of lymphoma.

Research done by a team of scientists from University of Pennsylvania shows that for first time the UPR is active in patients with human lymphomas and mice genetically bred to develop lymphomas. Importantly, when the UPR is inactivated, lymphoma cells readily undergo cell death.

"The general implications of work are that components of this pathway may be attractive anti-tumour targets, especially in lymphomas," says Koumenis. "Indeed, an enzyme called PERK, a kinase that we found to play a central role in UPR, is already being targeted by academia, pharma companies with specific inhibitors."

The cancer-causing gene c-Myc paradoxically activates both cell proliferation and death. When the cell becomes cancerous, c-Myc-induced death is bypassed, promoting tumor formation. "A critical feature of c-Myc-overexpressing cells is an increased rate of protein synthesis that is essential for Myc's ability to cause cancer," says Tom Cunningham, a post doctoral fellow in the Ruggero lab. "Myc tumor cells use this aberrant production of proteins to block apoptosis and activate the UPR. These cancer cells depend on Myc-induced increases in protein abundance to survive. Therefore, targeting protein synthesis downstream of Myc oncogenic activity may represent a promising new therapeutic window for cancer treatment," adds Ruggero.

The accumulation of unfolded proteins in the endoplasmic reticulum, an inner cell component where newly made proteins are folded, initiates a stress program, the UPR, to support cell survival. Normally, UPR kicks in when there is an imbalance in the number of proteins that need to be folded and chaperones, specialized proteins that help fold them.

An analysis of mouse and human lymphomas demonstrate higher levels of UPR activation compared with normal tissues. Using multiple genetic models, the two teams, in collaboration with additional labs in the US and Europe, demonstrated that Myc specifically activated one arm of the UPR, leading to increased cell survival by autophagy.

Autophagy is a survival pathway allowing a cell to recycle damaged proteins when it's under stress and reuse the damaged parts to fuel further growth. Cancer cells might be addicted to autophagy, since this innate response may be a critical means by which the cells survive the nutrient limitation and lack of oxygen commonly found within tumours.