"We've shown that cancer cells can adapt to the problemscaused by stress, by hijacking normal cell waste disposal to 'bag up and bin'toxic proteins," says Prof. Margaret Frame, a Cancer Research UK scientist atthe
Edinburgh Cancer Research UK Centre. "This reveals a previously unknownweak spot in cancer cells—and a potential new pathway to tackle cancer.Combining drugs already in development, which block a protein called FAK, withtechniques to stop cancer cells removing excess toxic SRC, would kill them."
The study reports a mechanism for the regulation of activeSrc in cancer cells. Although "classical" autophagy can be induced via serumand nutrient starvation irrespective of FAK status, it is only in the absenceof FAK, or disruption of integrin signaling through the FAK/Src pathway, thatactive Src is selectively targeted to autophagic puncta.
Engagement of this autophagy pathway allows these cancercells to "cope with" the stress of excessive, "untethered" Src activity andavoiding loss of viability. Importantly, equivalent FAK-proficient cancer cellsare not similarly dependent on Src-selective autophagy for their survival,exposing a previously unrecognized cancer cell vulnerability, according to theresearchers.
"This study has potential implications for the use of FAKinhibitors that are now undergoing clinical testing; it may be thatsimultaneous treatment with FAK and autophagy inhibitors could providetherapeutic benefit in some contexts," the researchers concluded. "Theexperiments we report in mouse pancreatic tissue demonstrate that autophagictargeting of active Src occurs in different tissue types and
in vivo, implyingthat this is a common mechanism to cope with the stress of impaired fluxthrough the integrin/Src/FAK pathway. It may also explain why FAK is commonlyco-upregulated with Src in epithelial cancers, ensuring that flux through thepathway is appropriately maintained."
Cancer Research UK's network of more than 4,000 scientists,doctors and nurses support all research into all aspects of cancer.
"Thanks to the generosity of the public's support we're ableto invest in world-leading research such as this. By learning more about howcancer cells cheat death, we hope we'll discover new ways to prevent and treatthe disease," said Dr. Julie Sharp, Cancer Research UK's senior sciencecommunications manager, in a statement.
