Abstract 2653: Non-muscle myosin II a role in breast cancer proliferation, invasion and metastasis

Abstract We recently identified non-muscle myosin IIa (NMIIA) as a novel binding partner for HER3 in HER2+ breast cancer cells. This interaction was observed through HER3 immunoprecipitation experiments following inhibition of the HER family, compared to vehicle control treatments. NMIIA, a hexameric protein, is encoded by the Myosin heavy chain 9 (MYH9) gene, which provides the heavy chain necessary for its structure and function. NMIIA plays a critical role in cytoskeletal dynamics and cellular mechanotransduction, processes implicated in cancer progression and metastasis. To investigate the clinical significance of NMIIA, we analyzed its protein expression in early-stage invasive breast cancer samples using immunohistochemistry. Tumor samples were stained with an antibody against NMIIA and subsequently stratified into two groups: the lower 50% and the upper 50% based on NMIIA expression levels. This stratification was performed by a trained pathologist. Focusing on patients with lymphovascular invasion (LVI), we found that those with high NMIIA expression levels exhibited significantly worse disease-specific survival compared to patients with low NMIIA levels (p = 0.010). Interestingly, no difference in survival was observed among LVI-negative patients, regardless of NMIIA expression levels (p = 0.948). These findings underscore a potential interplay between NMIIA expression and tumor vasculature, suggesting NMIIA may contribute to tumor progression in the presence of LVI. Ongoing studies aim to determine whether NMIIA is more highly expressed in matched brain metastases of breast cancer compared to their primary tumors, mirroring a pattern previously reported for HER3. This research will help elucidate NMIIA's role in metastatic progression and its potential as a therapeutic target. Additionally, we are exploring whether NMIIA contributes to breast cancer development in a mechanically sensitive manner using a novel parent NMII inhibitor compound. This compound has already led to the development of a small molecule inhibitor that has entered clinical trials, highlighting the translational potential of targeting NMIIA. Our findings suggest NMIIA as a key player in HER3 signaling and tumor progression, particularly in the context of LVI, and provide a foundation for further research into its mechanistic and therapeutic implications. Citation Format: Wasim Feroz, Sarah Storr, Andrew Stiles, Marykate Kilroy, Olamide Ogunleye, Joan T. Garrett. Non-muscle myosin II a role in breast cancer proliferation, invasion and metastasis [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 2653.