Monash scientists shed light on mystery protein linked to prostate cancer

Prostate cancer is the most common male cancer in Western societies and the third most common cause of cancer-related mortality.

One in six men in Australia are at risk of developing prostate cancer by the age of 85, according to the Cancer Council of Victoria.

Prostate cancer is the most common male cancer in Western societies and the third most common cause of cancer-related mortality.

In recent years scientists have been looking at the role of a protein called Cysteine-rich secretory protein 3 (CRISP3) in prostate cancer.

They know that higher levels of CRISP3 are linked to poor prognosis, but its role in cancer was completely unknown. Specifically is it a driver of prostate cancer or is it merely a bystander that it upregulated as part of an unrecognised disease process?

Now, new research on CRISP3 published in Endocrine-Related Cancer and led by male infertility expert Professor Moira O’Bryan from the Monash School of Biological Sciences and Dr Luc Furic from the Monash Biomedicine Discovery Institute has identified CRISP3 as a driver of prostate cancer progression from the so-called indolent state into aggressive disease.

“CRISP3 expression is very low in the normal human prostate, but is frequently over-expressed up to 2000-fold in malignant prostate samples,” said Professor O’Bryan.

“While there is unequivocal evidence that CRISP3 is associated with a range of physiological states, including prostate cancer, the function of CRISP3 in these processes had not been tested.

“Our work addresses a critical question relating to CRISP3 in prostate biology; does CRISP3 have a pro-tumorigenic role (producing more dangerous tumors) in prostate cancer: and if yes, what is its mode of action?”

To answer these questions the research team produced a unique animal model and examined prostate cancer cells from mice and humans.

They have discovered, for the first time, that the over-production of CRISP3 leads to a transition from isolated disease into invasive prostate cancer. Both the type of cancer and its volume are worsened in the presence of CRISP3.

Specifically, the researchers have shown that CRISP3 over-production is a step in the transition from in situ carcinoma to invasive prostate cancer.

To do this, the researchers produced a prostate cancer prone mouse model where CRISP3 was either present or missing from the prostate, and showed that mice missing CRISP3 were protected from this critical transition in prostate cancer disease progression.

Further, they demonstrated that CRISP3 promotes carcinogenesis by triggering the up-regulation of adhesive proteins on cells that result in what is known as an epithelial-to-mesenchymal transition, and thus, a ‘pro-invasive’ state.

These findings will need to be further validated in large cohort of men with prostate cancer to demonstrate the prognostic value of CRISP3 expression to identify men with high risk disease.

Future work will also focus on testing if CRISP3, or key proteins it regulates, could be valuable targets for intervention in patients with aggressive disease.

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