Expression and prognostic relevance of MACC1 in breast cancer cells
PhD student: Jasminka Mujic-Prguda
The variations in morphologies, differences in metastatic behavior and in the response to therapeutic treatments make breast cancers hard to treat. Basal-like/triple negative breast cancer is a subtype of breast cancer that does not express any of the possible receptors (ER, PR, and HER2) and patients diagnosed with basal breast cancer face a challenge in treatment since they cannot be treated with endocrine therapy. It is necessary to elucidate the possible signaling pathways that could serve as a potential therapeutic targets and, at the same time, also be a biomarker for early detection no matter which subtypes patients are diagnosed with. The newly identified proto-oncogene MACC1 gene (Metastasis-Associated Colon Cancer 1) is a prognostic marker for the detection of metastases in primary tumors of colon cancer. MACC1 stimulates proliferation, motility and invasion in colon cancer cells through upregulation of c-MET. Once activated, c-MET can result in the activation of several downstream signaling cascades (MAPK and PI3K/Akt pathways). The MACC1 was first identified to be overexpressed in primary and metastatic tumor tissue of colon cancer compared to healthy tissue. Recent studies have shown that the MACC1 gene is upregulated in different types of tumors such as lung cancer, adenocarcinoma, gastric cancer and hepatocarcinoma. Additionally, in past years a large number of clinical studies have described c-Met receptor overexpression and pathway hyper-activation in tissue derived from breast cancer patients. Furthermore there are no studies addressing the activation pathway of MACC1 in breast cancer. Our aim is to elucidate the role of the MACC1 gene in this cascade and it's correlation with c-MET expression and relationship with the tumor progression in breast cancer cells. Hence, the MACC1 gene could play a key role in differentiation, migration and invasion of breast cancer cells and serve as a potential therapeutic target.
