Research Projects

Metastatic breast cancer is a prevalent disease that often results in fatalities due to the lack of effective anti-metastatic chemotherapies. The role of metastasis-associated signalling proteins in breast cancer dissemination is not fully understood, making it a top aggressive cancer in India, particularly in the North-eastern States. The RNA binding protein HuR (ELAVL1) is significantly associated with metastatic events in various cancers, including breast cancer. HuR is often upregulated in metastatic cancers and plays a role in post-transcriptional regulation of tumor-associated genes. Its expression is higher at all stages of breast cancer and is linked to poor prognosis. Several small molecule inhibitors against HuR have been identified, but they have not progressed through preclinical trials. In the context of breast cancer, MS-444, dihydrotanshinone, and quercetin have been reported to have anti-cell migratory effects. The project proposal aims to synthesize a series of HuR inhibitors after molecular modeling, evaluate their toxicity and anti-cancer effects using normal noncancerous and metastatic breast cancer cell lines, and conduct cell migration and 3D invasion assays to test their anti-metastatic effects. Based on preliminary studies and literature review, the authors believe that HuR is an important target for blocking breast cancer cell metastasis and should be considered for novel anti-metastatic drug discovery. The proposed project has several translational directions for identifying novel HuR-inhibitors as effective anti-metastatic chemotherapeutic agents against metastatic cancers and shedding light on the cellular mechanisms of the RNA binding protein HuR in normal and cancer cell functions.