The “dark molecule” – meaning it’s understudied – is known as ‘Protein Serine Kinase H1’ (PSKH1) and is associated with tumour progression and metastasis. However, until now, how it does this has been unknown.

In this study, published in the journal PNAS and led by WEHI and the Monash Institute of Pharmaceutical Sciences (MIPS), the team uncovered the way in which PSKH1 is activated (or “switched on”) and, importantly, how it is switched off.

In the case of PSKH1, which is a ‘signalling molecule’, the researchers found that when it binds to a protein called ‘Calmodulin’ PSKH1 is “switched on” and when it binds to a protein called ‘Reticulocalbin’ it is “switched off”.

Joint senior author, Dr John Scott from MIPS, describes the signalling activity as “a balancing act within our cells.”

“Tumours form because cells ignore normal signals that tell them it’s time to stop growing, or that it’s time to die. When a signalling protein, such as PSKH1, interacts with certain proteins on a cell surface, this binding triggers a chain of events that can amplify the cell activity and lead to the formation of tumours,” Dr Scott said.

“Now that we know more about the proteins driving the “on” and “off” status of PSKH1, we can start to develop new drugs that target this molecule and, ultimately, improve therapies for prostate and other cancers.”

In 2024, prostate cancer was estimated to be the most commonly diagnosed cancer for males and for Australia overall. Treatments such as hormone therapy and chemotherapy can be effective, yet the side effects can be debilitating.

Joint senior author, WEHI deputy director Professor James Murphy, said the teams’ goal is to harness this new information to develop better, more targeted therapeutic approaches.

“Switching off PSKH1 essentially means being able to stop the progression of implicated cancers in their track, and thereby this new information opens up a whole new world of potential when it comes to developing new drugs,” Professor Murphy said.

Lead author Dr Chris Horne from WEHI said that understanding the mechanisms of how to switch PSKH1 on and off can also be applied to other molecules within the same family, which broadens the potential of the study’s findings to other cancers and disease.

“From here, our goal is to explore how we can start to develop new, effective therapies for signalling proteins, such as PSKH1, with fewer side effects,” said Dr Horne.