Canadian researchers have just discovered a molecular mechanism that drives cancer progression, providing the possibility for the use of precision medicine whereby patients are matched to drugs to which they are most likely to respond. Findings were published in Cancer Research.
A team of biochemists at Université de Montreal found that a group of enzymes called SRC kinases chemically modify a tumour-suppressing protein called SOCS1. “SOCS1 is part of a gene-regulation circuit centred around the master cell proliferation regulator p53, often called the guardian of the genome," said senior author Gerardo Ferbeyre, an UdeM biochemistry professor and researcher at its hospital research centre, the CRCHUM. “If p53 or another protein in its network is mutated or becomes chemically modified in some abnormal way, a pattern of gene activation occurs that programs cells to proliferate without control, as occurs in cancers.”
The therapeutic implications of these findings are hugely significant. Effective anticancer drugs that target SRC kinases already exist but the detection of modified SOCS1 in a tumour could be used to predict whether these drugs would be an effective treatment for the tumour.
“We were able to detect phosphorylated SOCS1 in patients' samples with an antibody that we developed,” said UdeM PhD student Emmanuelle Saint-Germain. “The same antibody could be used to detect phosphorylated SOCS1 in a clinical setting, providing a way to decide whether SRC kinase inhibitors would be an effective treatment.”
“This new mechanism for SOCS1 inactivation may actually represent a regulatory control that is hijacked by cancer cells,” said Université de Sherbrooke biochemist Subburaj Ilangumaran. “On a more fundamental level, our group's discovery - that phosphorylation of SOCS1 acquires a new physical form - opens the door to hitherto unknown ways of regulating SOCS1 functions.”