Researchers find clue to cancer cell survival

Protein and cell biology research at The University of Western Australia has contributed to a groundbreaking international study that demonstrates a way to alter the survival of cancer cells.

The work demonstrates, for the first time, that the active sarcoma (Src) gene product is differentially targeted in cancer cells to maintain the viability of the cancer cells.

The results of the research ‘Autophagic targeting of Src promotes cancer cell survival following reduced FAK signalling’, led by Professor Margaret Frame at the Edinburgh Cancer Research UK Centre, have been published on Nature Cell Biology's website.

Research reagents, prepared by Professor Wally Langdon from the UWA School of Pathology and Laboratory Medicine, were used to help determine the mechanism by which another cancer-causing protein, called Cbl, contributes to this process. Cbl was found to sequester active Src and direct its trafficking and degradation by a process known as autophagy. Importantly, if autophagy was inhibited by deleting the Cbl protein then cancer cell death occurred.

Considerable evidence now links increased activity of Src to cancer development and this study has revealed new ways in which Src is regulated in cancer cells. This raises additional strategies for targeting signalling pathways in cancer cells, for example by the use of autophagy inhibitors. Professor Langdon said the joint research represented a significant step in understanding the way cancer cells respond to high levels of activated Src.

“The evidence suggests that Src influences the life or death decisions that cells make and so by affecting the localisation of this protein in cancer cells we can alter cell responses that are often found in cancer.”

The finding raises new possibilities for drugs that not only inhibit Src's kinase activity but also drugs that determine where Src is localised in the cell, which ultimately determines its fate as a functional protein.