Abstract PO2-28-02: ROR1 regulates CREB3L1 via a novel signaling pathway in triple negative breast cancer

Abstract Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer; it is highly metastatic and incredibly difficult to treat due to its lack of the hormone receptors (estrogen, progesterone, and human epidermal growth factor receptor 2) that are used as therapeutic targets to treat breast cancer patients. TNBC patients are left with limited treatment options besides potent chemotherapy drugs that often leave them with undesirable side effects. My work intends to reveal a novel oncogenic signaling pathway that could be used to specifically target and eliminate TNBC in patients. Our lab is focused on a surface receptor that is found to be highly expressed only in cancerous tissue and during fetal development, Receptor tyrosine kinase-like orphan receptor 1 (ROR1). TNBC patients with high ROR1 expression are found to have poor prognosis and decreased overall survival rate compared to patients with low expression. ROR1 is thought to be a good drug target because it activates various oncogenic pathways such as PI3K/AKT and STAT3 in order to increase TNBC metastasis and chemoresistance. Previous single cell RNA sequencing data showed that TNBC tumors with high ROR1 expression also had reduced expression of cAMP responsive element binding protein 3 like 1 (CREB3L1). Often TNBC patients are found to have low CREB3L1 expression, a transcription factor is thought to play a tumor suppressive role in TNBC by increasing the expression of genes associated with the unfolded protein response (UPR) when ER stress occurs. CREB3L1 silencing in TNBC is due to hypermethylation of its promoter region by DNA methyltransferases (DNMTs). We hypothesize that ROR1 regulates CREB3L1 by influencing DNMT activity. This project aims to reveal the tumor suppressors that are downregulated in TNBC by ROR1 activation. Citation Format: Victoria Reed, Eric Lalu, Bela Peethambaran. ROR1 regulates CREB3L1 via a novel signaling pathway in triple negative breast cancer abstract. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-28-02.