While organ confined cancer can be treated effectively by surgical removal of the tumour, the same is not true for cancer that has spread (metastasised). For these patients, prognosis is poorer and drops significantly the later diagnosis occurs. In fact, greater than 90% of cancer deaths result from metastasis. Due to its complex molecular nature, it has been difficult to identify proteins critical in metastasis.

Our group and other laboratories have shown that a cell surface protein known as CUB domain containing protein 1 (CDCP1) can assist cancer cells to spread. We have shown that CDCP1 does this by helping cells to evade cell death (apoptosis) during a key stage of metastasis – as the cancer cells escape from blood vessels. Importantly, very recently using two animal models, we have shown that an antibody that specifically recognises CDCP1 can inhibit the spread of cells. Our data indicate that an antibody binding to CDCP1 prevents cells from evading cell death as they exit from blood vessels.

Significance: We propose that CDCP1 may be a suitable target for inhibiting the spread of cancers in which this protein is dysregulated, including bowel cancer. In particular, CDCP1 may be a useful target for inhibiting the spread of cancer cells that are in the blood system after a patient has undergone surgery to remove a primary tumour. Our current work needs to be extended to cells from other cancers and more information is needed on how CDCP1 helps in evasion of apoptosis and how targeting of CDCP1 induces cell death.

We hypothesise that CDCP1 helps cells from a range of cancers to evade apoptosis by relaying pro-survival signals from the outside to the inside of cells. We propose that antibody binding to CDCP1 prevents the relay of pro-survival signals and results in death.

The aims to test these hypotheses are to:

1. Examine the ability of CDCP1 to facilitate evasion of apoptosis in cells from a range of cancers.
2. Characterise the pro-survival signals relayed by CDCP1 and blocked by antibody binding.

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