The CCB’s Cell Signalling Laboratory, headed by Adjunct Associate Professor Yeesim Khew-Goodall, in collaboration with a research group headed by Monash University’s Professor Roger Daly, have discovered some of the key enzymes that control the secretion of metastasis-promoting proteins.
Dr Khew-Goodall says cancer cells can stimulate metastasis by secreting signalling proteins that interact with both their local environment to trigger cancer cell migration and distant sites to pre-condition the secondary sites for colonisation, long before the cancer cells arrive.
“The mechanisms regulating the secretion of these signalling molecules are currently poorly understood,” she says.
“A deeper understanding of the mechanisms used by tumour cells to convert their secretion profile from that of a non-malignant cell to one that favours tumour progression and metastasis is therefore likely to be critical in combating metastatic disease.”
Using both cell culture approaches and verification in animal models, the researchers found that an enzyme that is mutated in various cancers has an important role in suppressing the secretion of signalling proteins, and identified the partner molecules through which the enzyme acts.
“We were able to demonstrate in mouse cancer models that the secretions from cancer cells that lack the enzyme could alone promote metastasis, and the cancer cells that lack the enzyme were more prone to metastasis, suggesting that boosting the level of the enzyme could block cancer metastasis,” Dr Khew-Goodall says.
“We further found that patients who have cancers with low amounts of the enzyme are more at risk of metastasis.”
The discovery is published in prestigious international journal Science Signaling.
