Researchers at Sinai Health have discovered that a single protein allows them to divide all types of cancer into two superclasses depending if the said protein is activated or not. The presence or absence of this protein might have some important consequences in treating this wide and complex range of diseases – cancer is an umbrella term covering many diseases affecting almost any tissue or organ. It is the second leading cause of death globally.
As reported in the journal Cancer Cell, the team has discovered evidence suggesting that the Yes-associated protein (YAP) is either "on" or "off" in cancer cells, meaning the cell either does or does not produce it. This difference in protein expression leads to different drug sensitivity and resistance.
YAP helps regulate Hippo signaling, the pathway that controls organ size and cell growth. Dysregulation of this pathway contributes to the unconstrainted growth of cancer. The YAP configuration as "on" or "off" has different effects.
“Not only is YAP either off or on, but it has opposite pro- or anti-cancer effects in either context,” senior author Rod Bremner, from the Lunenfeld-Tanenbaum Research Institute (LTRI), part of Sinai Health, said in a statement. “Thus, YAPon cancers need YAP to grow and survive. In contrast, YAPoff cancers stop growing when we switch on YAP.”
The team’s work highlights that many YAPoff cancers have a high mortality rate, and that some cancers – such as prostate and lung cancers – might switch from a YAPon to a YAPoff configuration, becoming harder to deal with.
“The simple binary rule we uncovered may expose strategies to treat many cancer types that fall into either the YAPoff or YAPon superclasses,” Joel Pearson, co-lead author of the research, explained. “Moreover, since cancers jump states to evade therapy, having ways to treat either the YAPoff and YAPon state could become a general approach to stop this cancer from switching types to resist drug treatments.”