2024 AIChE Annual Meeting
CRISPR Facilitated Knockout of RPL39 & RPL39L, Implications for TNBC Metastasis
Breast cancer stem cells (CSCs) represent a subpopulation of cells within tumors with enriched tumorigenic potential and heightened resistance to both radiation and chemotherapy. Previous work in the Chang lab demonstrated an enriched CSC gene signature post-chemotherapy, suggesting that these cells are selected for by standard therapy. shRNA screening of this 493-count gene signature in MpBC cell lines identified ribosomal protein 39 (RPL39) and its paralog RPL39-Like (RPL39L) as key genes involved in CSC self-renewal, treatment resistance, and lung metastasis. Based on preliminary data showing higher CSC numbers and RPL39 expression in Metaplastic Breast Cancer (MpBC)s compared to non-MpBC Triple Negative Breast Cancers (TNBCs) and considering RPL39 and RPL39L was originally identified from a CSC gene signature, this proposal addresses whether differential expression of RPL39 and RPL39L ribosomal proteins preferentially translates proteins causing the aggressive and chemorefractory nature of MpBC using CRISPR knockout (KO) technology. Crispr-Cas9 was successfully employed, resulting in complete losses of RPL39 and RPL39L function in separate cell lines. Future work involves characterization of stem-cell properties to precisely determine these genes' role in cancer metastasis.