Molecular Pathway involved in Breast Cancer Tumor Cell Dormancy Escape in the Bone Marrow
Panzica, Louis Philip, Jr.
MetadataShow full item record
Cancer tumor cell dormancy is a significant clinical problem in breast cancer. Many patients present detectable disseminated tumor cells at an early stage but not all of these patients will have recurrence. Also, some patients do not have detectable disseminated tumor cells but will have a recurrence years later. This poses the idea that dormancy is a major factor in cancer, but to this day there remains no methods to accurately detect and treat these cells. In this study we use a dormancy assay to develop a list of suppressed genes that allow breast cancer cells to escape dormancy in the hematopoietic stem cell niche of the bone marrow. We use this list to rank genes based on their probable interaction with the previously confirmed dormancy gene, p38, and their role in metastasis. From known upstream or downstream genes, we were able to come across Wnt3 as a potential signaling protein inducing this dormant phenotype. Using breast cancer cells normally dormant in the hematopoietic stem cell niche (the endosteal niche), MDA-MB-231, we were able to confirm that knockdown or through natural inhibition of WNT3, causes escape from dormancy and induces proliferation. Furthermore, in breast cancer cells that normally overcome the dormant effects of the endosteal niche and actively proliferate, WNT3 overexpression returns them back to a dormant state, suppressing their proliferation. The significance of this study is to determine signaling pathways that interact to induce a dormant state of breast cancer cells in the bone marrow. By understanding the molecular mechanisms of these cells, treatments could be developed to actively target them and prevent disease recurrence. We hypothesize that the loss of genes, such as WNT3, may be activating Myc targets, allowing for an escape from dormancy and ultimately causing a bone metastasis.