Lorne 2012: Flipping cancer’s switch

It seems the more we learn about fighting cancer, the more the cancer cells learn about resisting. But the fight is far from over, with researchers like Dr Nikki Verrills working on finding new ways to ‘re-arm’ a key signalling switch that gets turned off in cancer cells, enabling them to proliferate.

Verrills is a Cancer Institute NSW Early Career Researcher Fellow at the University of Newcastle where her research group studies signalling in cancer. Specifically, she aims to understand how protein phosphatases act as tumour suppressors in cancer progression and chemotherapy resistance, with a focus on breast cancer and leukaemia.

Verrills has always been interested in the area of resistance to chemotherapy, starting with her PhD work in the area of childhood leukaemia, where she used a protein biochemistry and proteomics approach to compare proteins between patients who responded to chemotherapy and those that did not.

Verrills then moved to Newcastle for postdoctoral work and to a lab that was interested in phosphatases in asthma and neuroscience. Coming from the cancer field and knowing of the link between signalling and cancer, she was keen to marry the two areas together.

At the Lorne Conference on Protein Structure and Function in February, Verrills will describe recent and exciting work on her protein phosphatase of choice, PP2A, and how reactivating it in some leukaemia patients may block the cancer’s progress, particularly those leukaemias that respond poorly to current treatments.

Protein phosphatases are signalling enzymes that specifically remove phosphate groups from cellular proteins to modulate their function (dephosphorylation). Phosphatases usually team up with their opposing-acting enzyme, the protein kinases, in a phosphorylation/dephosphorylation mechanism that is critical to regulate all sorts of cellular functions including growth, metabolism and cell death.

Dysfunction of these mechanisms are also implicated in many abnormal cell processes such as the transformation of a normal cell into a cancerous one and the sneaky tricks that cancer cells develop to resist the effects of chemotherapy.

“Over the past 15-20 years, a huge amount of research has been done looking at these signalling pathways in cancer cells, although most of that centred on the protein kinases that do the phosphorylating,” says Verrills.

“From that, we know that these enzymes are extremely important in cancer development and, indeed, some kinases are now targets for many molecularly targeted anti-cancer drugs. There has been a lot less done on the phosphatases, but from research in the past decade it seems that to get certain cancers going you need not only overactivation of the protein kinases but, at the same time, inactivation of the phosphatases – hence their classification as tumour suppressors.”

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