Abstract
Abstract Metastasis is cancer’s lethal driver. Metastatic cancer cells leave the primary tumor and travel through the blood stream to distal sites. These cancer cells are aggressive, highly recurring and pose challenges for clinical treatment. There is a critical need to define drivers of metastasis in order to identify novel drug targets and improve patient prognosis. Our previous work identified a potential breast cancer metastasis promoting gene known as PHLDA2. By single cell RNA sequencing, PHLDA2 gene expression was elevated in metastatic lesions compared to primary breast tumor tissue. This gene has not previously been linked to cancer metastasis; therefore, the objective of the current study is to confirm PHLDA2 as a driver of breast cancer metastasis and define the mechanisms by which it exerts its pro-metastatic function. We manipulated multiple breast cancer models to have elevated or reduced PHLDA2 levels to investigate its role in metastasis. We have additionally explored the mechanism of PHLDA2 in metastasis at the RNA level by qPCR, the protein level by western blot analysis, and the organ level using immunofluorescence staining and bulk sequencing. We confirmed using our breast cancer models of elevated or reduced PHLDA2 expression that PHLDA2 has a pro-metastatic function. Bulk RNA sequencing data revealed that PHLDA2 promotes extracellular matrix (ECM) remodeling. This finding is significant as ECM remodeling plays a critical role in cancer progression and metastasis. Investigation of PHLDA2’s pro-metastatic function is necessary to gain deeper insights into the mechanisms of cancer cell spread and reveal novel drug targets to improve patient survival. Citation Format: Paige Halas, Hannah Savage, Dennis Ma, Jacob Insua-Rodriguez, Sharmila Mallya, Connie Chan, Radhika Domadia, Tatyana Lev, Devon Lawson. Investigating PHLDA2 as a Genetic Driver of Breast Cancer Metastasis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr B003.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
