Presenter Information

Ariadna Daniela MenjivarFollow

Presentation Type

Oral/Paper Presentation

Abstract

Our lab is investigating the protein Neprilysin (NEP) and its role in Triple-Negative Breast Cancer (TNBC). Previous bioinformatics data from Dr. Conway’s research indicated that in TNBC cells high in Neprilysin expression (HCC38), the PI3K pathway was the most active signaling pathway. This information suggests that Neprilysin is positively upregulating the PI3K pathway in this cell line. This is interesting given the fact that in the context of TNBC, Neprilysin has been shown to negatively regulate the PI3K/AKT signaling pathway. The PI3K/AKT pathway is the most commonly mutated pathway in breast cancer. AKT is the central mediator protein in this pathway and had 3 distinct isoforms. While AKT is primarily characterized as a cancer-promoting protein, the AKT-1 isoform has been shown to inhibit breast cancer invasion. Therefore, we are interested in understanding the functional significance of NEP and P13K-AKT signaling. In this project, we conducted invasion assays to test our hypothesis that Neprilysin expression alters sensitivity to drugs targeting the PI3K pathway by regulating AKT1 activation. Our results indicate NEP knockdown significantly increases breast cancer cell invasion. Importantly, we also found that cells lacking NEP are more sensitive to PI3K inhibition than cells expressing NEP. These results highlight the potential role of NEP in modulating the balance between AKT isoforms. Our hypothesis that AKT-1 is regulated directly by NEP still needs to be further investigated through western blotting and immunoprecipitation, which is our current focus. This information would be critical for understanding Triple Negative Breast Cancer cell behavior.

Faculty Mentor

Dr. Beth Conway

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Exploring the Functional Role of Neprilysin in PI3K/AKT1 Signaling in Triple-Negative Breast Cancer

Our lab is investigating the protein Neprilysin (NEP) and its role in Triple-Negative Breast Cancer (TNBC). Previous bioinformatics data from Dr. Conway’s research indicated that in TNBC cells high in Neprilysin expression (HCC38), the PI3K pathway was the most active signaling pathway. This information suggests that Neprilysin is positively upregulating the PI3K pathway in this cell line. This is interesting given the fact that in the context of TNBC, Neprilysin has been shown to negatively regulate the PI3K/AKT signaling pathway. The PI3K/AKT pathway is the most commonly mutated pathway in breast cancer. AKT is the central mediator protein in this pathway and had 3 distinct isoforms. While AKT is primarily characterized as a cancer-promoting protein, the AKT-1 isoform has been shown to inhibit breast cancer invasion. Therefore, we are interested in understanding the functional significance of NEP and P13K-AKT signaling. In this project, we conducted invasion assays to test our hypothesis that Neprilysin expression alters sensitivity to drugs targeting the PI3K pathway by regulating AKT1 activation. Our results indicate NEP knockdown significantly increases breast cancer cell invasion. Importantly, we also found that cells lacking NEP are more sensitive to PI3K inhibition than cells expressing NEP. These results highlight the potential role of NEP in modulating the balance between AKT isoforms. Our hypothesis that AKT-1 is regulated directly by NEP still needs to be further investigated through western blotting and immunoprecipitation, which is our current focus. This information would be critical for understanding Triple Negative Breast Cancer cell behavior.

 

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