"Our data offer a new way to think about cancer, adding to the current paradigm," says Gavin MacBeath, an assistant professor of chemistry and chemical biology in Harvard's Faculty of Arts and Sciences and co-author of a paper published in the journal Nature. "We present the hypothesis that an important component of oncogenesis is the ability of proteins to turn on alternative, secondary signaling pathways when overexpressed, rather than simply upregulating primary pathways."
MacBeath and colleagues studied the four human ErbB receptors, which set in motion widely studied cellular processes including cell migration, adhesion, growth and death. These receptors span the cell membrane; the external portion binds free growth factors, creating biochemical signals propagated inside the cell.
Each ErbB receptor has multiple intracellular binding sites where proteins can dock, but MacBeath's group found that only two of the four ErbB proteins, known as EGFR and ErbB2, become dramatically more "promiscuous" -- able to recruit and activate a large number of different signaling proteins -- when present at high concentrations.
"These two promiscuous ErbB proteins are known to be overactive in many human cancers, suggesting that their ability to turn on rampant signaling may contribute to their high oncogenic potential," MacBeath says. "This newfound link may also offer alternative strate
Contact: Steve Bradt