Abstract 2649: Defining how Rnd3, a novel regulator of breast cancer invasion, affects the metastatic potential of triple-negative breast cancer

Abstract The purpose of this study is to investigate whether the atypical Rho GTPase, Rnd3, affects triple-negative breast cancer (TNBC) cells metastatic potential (invasion and migration rates). One of the most dangerous attributes of cancer is its ability to metastasize and spread. The 5-year survival rate for localized breast cancer is 90%. However, this drops to 29% when breast cancer metastasizes. Identifying key regulatory proteins and signaling pathways involved in cell migration and invasion, two hallmarks of metastasis, will pave the way to potential therapeutic targets for reducing the metastatic potential of breast cancer. Rho GTPases regulate cellular processes that are commonly dysregulated in cancer with many studies focusing on what roles these proteins play in tumorigenesis. The expression level of the atypical Rho GTPase, Rnd3, rather than Rnd3 mutations, has been linked to cancer. High expression of Rnd3 increases cellular migration and invasion in several cancers, while depletion of Rnd3 decreases cellular proliferation and migration. How Rnd3 expression affects breast cancer progression is unknown. Here we assayed a panel of TNBC cell lines and assessed their migration and invasion potential, we observed a correlation of high Rnd3 expression and high cell migration and invasion rates. After knocking down Rnd3 expression in these cell lines we observed a significant reduction in cell invasion in MB-231, HCC1937, and MCF7 cells, and decreased cell migration in MB-231 cells. Rnd3 has been shown to regulate cell migration via the RhoA-ROCK1 pathway in melanoma. We were unable to rescue invasion rates in Rnd3 knockdown MB-231 cells following either chemical inhibition or knockdown of ROCK1, indicating Rnd3 is regulation cell invasion via a novel pathway in TNBC cells. Our findings indicate that Rnd3 regulates cell invasion and migration, two hallmarks of metastasis, in TNBC cells. Citation Format: Noemi Garcia Garcia, Thanh Ha Vy Nguyen, Dane Richey, Katie R. Ryan. Defining how Rnd3, a novel regulator of breast cancer invasion, affects the metastatic potential of triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2649.