Abstract 6372: Regulating epithelial-to-mesenchymal transcription-driven metastatic capacity with molybdenum disulfide (MoS2) nanoparticles.

Abstract Epithelial-to-mesenchymal transition (EMT) is the process by which stationery, tightly connected epithelial cells transform into more mobile, flexible phenotype. This plays a significant role in allowing cancer cells to detach from the original tumor, invade surrounding tissues and spread throughout the body. While EMT plays a role in significant physiological functions such as wound healing, the development of a mesenchymal phenotype within the tumor microenvironment is detrimental, promoting cancer cell escape into circulation and subsequent development of the pre-metastatic niche. EMT is a major contributor to the risk and progression of metastatic cancers and targeting and blocking EMT presents a potential therapeutic intervention for preventing the development of metastases. Here, we introduce molybdenum disulfide (MoS2) nanoparticles as a potential drug-free inhibitor of EMT, which is advantageous over traditional chemotherapy-type drugs due to lack of adverse off-target effects in distant tissues. This study investigates the impact of MoS2 nanoparticles on epithelial-to-mesenchymal transition in highly metastatic triple-negative breast cancer both in vitro and in vivo. Treatment of MoS2 nanoparticles decreased migratory capacity of in vitro and in vivo models of ER+ and triple negative breast cancer, demonstrating the anti-metastatic motility property of MoS2. In vitro, MoS2-treated breast cancer cells observe decrease in focal adhesion proteins and genes associated with cellular motility. Furthermore, cells show decrease in TGFβ signaling and expression of EMT markers after 72h of exposure, indicating that MoS2 nanoparticles inhibited EMT progression mediated through cellular motility and TGFβ signaling. This effect was further demonstrated with functional 3D mammosphere assays, which indicated reduced mammosphere formation and size. Similarly, clonogenicity was significantly reduced in cells following treatment with MoS2 nanoparticles. In vivo, direct injection of MoS2 into 4T1 mouse mammary tumors significantly decreased primary tumor growth and burden as well as the number of metastatic foci in the lung. Our work demonstrates that MoS2 nanoparticles inhibit integrin activity as well as the TGFβ signaling cascade pathway, blocking the transition of cells to a mesenchymal-like phenotype. These findings suggest that MoS2 nanoparticles hold promise for drug-free cancer therapeutic applications in reducing metastatic potential. Citation Format: Samantha Michelle Foster, Kanwar A. Singh, John Soukar, Olajumoke Ogunlusi, Christian Nguyen, Subiksha Sankar, Anna Keller, Tapasree Roy Sarkar, Irtisha Singh, Akhilesh Gaharwar, . Regulating epithelial-to-mesenchymal transcription-driven metastatic capacity with molybdenum disulfide (MoS2) nanoparticles abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6372.