Grant: Operating Grant

Breast cancer affects 1 in 9 women in Canada and accounts for about 15% of all cancer deaths in Canadian women. Metastasis is the spread of the tumor from the primary site of the breast and is a significant contributing factor to disease recurrence and patient mortality. We have been studying a protein called CREB3L1 that acts as a metastasis suppressor and is found in normal breast cells, as well as in breast cancers of low and medium grade, but is lost in highly metastatic breast cancers. CREB3L1 blocks expression of genes that promote cell growth, cell survival, new blood vessel formation and cell movement. Decreasing the CREB3L1 levels in poorly metastatic breast cancer cells enhanced metastatic properties. We have shown that re-introduction of CREB3L1 in highly metastatic breast cancer cells, which lack CREB3L1 expression, blocked metastasis and resulted in tumor regression. Thus, CREB3L1 is a metastasis suppressor, uniquely missing from highly metastatic breast cancer cells. We will expand our analysis from breast cancer cell lines to human breast tumor samples to better understand various factors that contribute to CREB3L1 levels. The difference in CREB3L1 levels will help us identify genes and/or molecular pathways that are needed for cell survival in these metastatic breast cancer cells that lack CREB3L1, but that are not essential in non-metastatic breast cancer cells or normal breast cells, both of which contain CREB3L1. We plan to test inhibitors of these identified gene targets for their ability to inhibit tumor development and/or metastasis. It is estimated that the majority (90%) of deaths due to breast cancer are caused by distant metastases. Our study will lead to new therapies that specifically target metastatic breast cancer cells. This will have a significant positive impact on treatment outcomes and survival that will improve the health of Canadians diagnosed with breast cancer.