Cancer can be caused solely¹ by protein imbalances within cells, a study of ovarian cancer has found. The discovery is a major breakthrough because, until now, genetic² aberrations³ have been seen as the main cause of almost all cancer. 

 

The research, published today in the journal Oncogene, demonstrates that protein imbalance is a powerful prognostic tool, indicating whether or not patients are likely to respond to chemotherapy and whether a tumour⁴ is likely to spread to other sites. 

 

The findings also open the possibility of new therapies aimed at measuring and preventing dangerous imbalances in cells. 

 

Lead author Professor John Ladbury, Dean of the University of Leeds' Faculty⁵ of Biological Sciences and Professor of Mechanistic Biology, said: "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 therapeutic⁶ approach. Our study demonstrates that genetic screening alone is not enough."

 

The research, led by scientists at the University of Leeds and The University of Texas MD Anderson Cancer Center, focused on the "Akt pathway," a signalling pathway within cells that drives cancer formation and the spread of cancers through the body.

 

Under normal conditions, the cell receives external signals through a cell wall-bound receptor (FGFR2 in this study). As a result of this stimulus⁷ the receptor is 'switched on' inside the cell. This results in the recruitment of signalling proteins and the initiation⁸ of the Akt pathway, which is responsible for committing the cell to proliferate⁹. In some cancerous cells, this pathway is permanently¹⁰ switched on. A conventional approach to diagnosing this cancer would be to look for genetic modification¹¹ of the receptor (or recruited proteins), which could be responsible for maintaining the switched on state.

 

The new study looked at isolated¹² cancer cells without external stimulation¹³ and found that the "Akt pathway" could be activated¹⁴ without genetic modifications¹⁵. Two proteins; Plcγ1 (pronounced "plc-gamma-1") and Grb2 (pronounced "grab-2"), compete for binding¹⁶ to FGFR2. The relative concentration of these proteins will dictate¹⁷ which one binds¹⁸. When Plcγ1 prevails, it triggers the Akt pathway. In this way, an imbalance in the amount of the two proteins can lead to cell proliferation and cancer formation.

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