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Triple-negative breast cancers (TNBCs) are tumors that lack the estrogen-receptor (ER), the progesterone-receptor (PR), and the epithelial growth factor receptor 2 (HER2) and are responsible for 15-20% of all breast cancer. TNBCs provide poor prognoses and higher rates for metastases compared to other breast cancers. We have found that cytoplasmic polyadenylation element binding protein 2 (CPEB2) mRNA splicing is dysregulated in cells that display resistance to anoikis (attachment-dependent cell death). Importantly, CPEB2A:B ratio decreases in patient-matched tumor tissue when compared to normal control tissue. Furthermore, downregulation of each isoform produced opposing effects on both AnR and HIF1alpha and TWIST1 levels (molecules that are downstream of CPEB2). Taken together, our results indicate that CPEB2 is involved in the development of anoikis-resistance in cancer cells and may be heavily involved in TNBC cancer progression. Additional studies of alternative splicing in TNBC may lead to both understanding of the molecular pathways leading to TNBC metastasis and the development of rationally designed treatments for TNBC.
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