Role of ESRP1/ESRP2 splicing regulators in the development of Triple-Negative Breast Cancer
Mentor: William Hahn, M.D. (Dana Farber Cancer Institute)
Breast cancer is a heterogeneous disease that differs greatly among patients. Specific biomarkers such as the expression of hormone receptors and HER2 determine the viability of targeted therapies and general prognosis of the disease. Breast carcinomas that positively express progesterone and estrogen receptors display to the best response to hormonal treatments and similarly, HER2-positive cancers have shown the best response to anti-HER2 targeted therapies. Breast cancers that do not positively express any of these biomarkers are referred to as triple-negative breast cancer (TNBC) and constitute one of the most genetically diverse subtypes overall. The lack of molecular understanding behind TNBC contributes to its limited treatment options and poor prognosis in comparison to other subtypes. This project will utilize CRISPR-Cas9 technology and lentiviral overexpression in the MCF10A human cell line model in order to explore the impact of splicing regulators on the development of triple-negative breast cancer. Studies will specifically investigate ESRP1 and ESRP2 splicing proteins in TNBC, as dysregulation of splicing factors governs many aspects of cancer biology but their specific role in breast cancer is still unclear. Exploring the molecular splicing mechanisms in this model will provide further insight into potential therapeutic targets that will contribute to the development of treatment for patients with the triple negative breast cancer subtype.
Figure 1. Mechanism of CRISPR/Cas9 genome editing. (Source: https://www.ncbi.nlm.nih.gov/books/NBK464635/figure/gen_edit.F2/) Source: