Abstract P3-01-24: The cancer-associated TRPC5 opposite strand protein, a novel regulatory factor for cell proliferation in triple negative breast cancer

Background: Breast cancer is the most common malignant tumors worldwide and the leading cause of cancer death among female. Microproteins, a kind of protein which is nearly 100 amino acids in length, have been demonstrated to play important roles in biology and disease. Here, we present a potential microprotein TRPC5 opposite strand (TRPC5OS), which may exert function in breast cancer progression. Methods: Differential expression of TRPC5OS in breast cancer was measured via Immunohistochemistry (IHC) in breast cancer samples and quantitative real-time PCR (qRT-PCR) in cell lines. The effects of TRPC5OS on proliferation and cell cycle progression of breast cancer cells were evaluated by using Cell counting kit-8 (CCK-8), colony formation assay and cell cycle analysis by flow cytometry. The tumor growth in vivo was observed in xenograft model. Co-immunoprecipitation (Co-IP), western blot analysis and immunofluorescent staining were performed to validate the interaction between TRPC5OS and ENO1. Glucose uptake was measured by liquid scintillation spectrometry and involvement of the PI3K and AKT pathways was investigated by western blot analysis. Results: TRPC5OS showed an enhanced expression in breast cancer patient samples predominantly in HER-2 negative breast cancer, especially in triple negative breast cancer (TNBC). Overexpression TRPC5OS increased TNBC cell proliferation, promoted cell cycle progression, enhanced xenograft tumor growth, and associated with PI3K-AKT pathway. In addition, TRPC5OS could enhance glucose uptake via interacting with alpha-enolase (ENO1) and increase the protein level of ENO1, and ENO1 was found to be the functional target of TRPC5OS in TNBC cells. Conclusions: This study demonstrates that TRPC5OS promotes proliferation by interacting with ENO1 and may provide a strategy for future diagnosis of human breast cancer, a new potential therapeutic target for TNBC patients as well. Key words: breast cancer, TRPC5OS, proliferation, ENO1, glucose uptake Citation Format: Yangyang Cui, Jinghui Peng, Yue Huang, Ziyi Fu, Hui Xie, Shui Wang. The cancer-associated TRPC5 opposite strand protein, a novel regulatory factor for cell proliferation in triple negative breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-01-24.