Protein imbalance in cells can cause non-genetic cancer

LEEDS, England, July 27 (UPI) — Cancer can be caused by protein imbalances in cells, according to a new study on ovarian cancer, showing that genetic mutations should not be the only focus for cancer researchers and clinicians.

The research also may help doctors determine if chemotherapy can be effective for all patients and whether tumors will grow or spread.

“There has been huge investment in sequencing the human genome with the idea that if we get all the relevant genetic information we can predict whether you have a predisposition to cancer and, ultimately, use a precision medicine-based approach to develop a therapeutic approach,” said Professor John Ladbury, dean of the Faculty of Biological Sciences at University of Leeds, in a press release. “Our study demonstrates that genetic screening alone is not enough.”

In normal cells, a cell wall receptor called FGFR2 attracts proteins that activate the Akt pathway, a part of the cell that helps it to proliferate. In some cells, this pathway is always on, motivating researchers to search for the responsible genetic mutation.

Researchers found in lab studies that two proteins compete to bind in the Akt pathway, Plcy1 and Grb2. When Plcy1 binds in the pathway, it activates cell reproduction, with Grb2 acting as a counter balance, controlling cell proliferation by only letting so many Plcy1 molecules bind. In cells with a deficiency of Grb2, cell growth has the potential to get out of control and become cancerous.

In lab tests with mice, researchers observed this and then counteracted the imbalance. Cells with depleted Grb2 grew uncontrollably but when levels of Grb2 were increased, growth was brought back under control.

After confirming the interaction of the two proteins, researchers examined data from The Cancer Genome Atlas, finding that high levels Grb2 relative to Plcγ1 and FGFR2 offered patients slightly better prognosis for recovery. Roughly 40 percent of of patients with the preferable balance survived seven years after tumor samples were taken, while less than 10 percent of patients with an unfavorable balance were still alive in that time.

“From the patient’s point of view, the key findings are that these proteins are biomarkers,” Ladbury said. “They could offer information to clinicians on who is going to benefit from therapy and, just as importantly, who is not. On the treatment side, the proteins’ interaction could be a valid therapeutic target: you could, for instance, target Plcγ1 to ensure it does not overwhelm the cell.”

The study is published in Oncogene.