What type of study is this?

This is a In Vitro Study study.

What question did this study set out to answer?

This research aims to explore how extracellular glucose levels influence the mechanical properties and invasive behavior of triple-negative breast cancer cells.

December 8, 2025

Abstract A012: Extracellular glucose level regulates cell mechanics and invasion of triple-negative breast cancer cells

Key Points

This research aims to explore how extracellular glucose levels influence the mechanical properties and invasive behavior of triple-negative breast cancer cells.
Utilized high-throughput mechanotyping assays to assess cell mechanics
Examined the effects of glucose levels on cell deformability and contractility
Inhibited GLUT3 to investigate impacts on glucose uptake and cancer cell properties
Elevated glucose levels decreased deformability and increased contractility of cancer cells
GLUT3 inhibition reduced glycolysis and ATP production
Altered mechanical properties diminished cell motility and reduced lung metastasis in vivo

Abstract

Abstract Cell mechanics, defined by deformability and contractility, play critical roles in cancer metastasis, yet the soluble cues and molecular pathways linking the tumor microenvironment to these mechanotypes remain poorly understood. Glucose availability varies widely between circulation, normal tissue, and tumor tissue, and cancer cells adapt through metabolic reprogramming that impacts growth, invasion, and epithelial–mesenchymal transition. Here, we investigate how glucose levels and glucose transport influence breast cancer cell mechanics and metastatic behavior, with a focus on triple-negative breast cancer (TNBC). Using high-throughput mechanotyping assays, we demonstrate that elevated extracellular glucose (5 mM) decreases deformability and increases contractility of breast cancer cells in a concentration-dependent manner through F-actin rearrangement and non-muscle myosin II (NMII) activation. Mechanistically, this is driven by the cAMP–RhoA–ROCK–NMII signaling axis, while calcium and MLCK are dispensable. In TNBC, we further identify glucose transporter 3 (GLUT3) as a key mediator of this response: GLUT3 inhibition by the selective inhibitor G3iA reduces glucose uptake, glycolysis, and ATP production, leading to AMPK activation, suppressed myosin activity, and impaired invasion. GLUT3 inhibition also activates the cAMP–PKA–VASP pathway, reducing F-actin levels and stiffness as measured by Atomic Force Microscopy, and increases YAP phosphorylation with reduced transcriptional activity. These mechanical alterations diminish motility in vitro and lung metastasis in vivo. Together, our findings establish a mechanistic link between glucose metabolism, cellular mechanotypes, and metastatic progression in breast cancer, highlighting the potential of integrating glucose control and mechanotype-targeting strategies into therapeutic approaches, particularly for TNBC. Citation Format: Aadil Qadir Bhat, Seeun Oh, Jun-Yong Choe, Tae-Hyung Kim. Extracellular glucose level regulates cell mechanics and invasion of triple-negative breast cancer cells abstract. In: Proceedings of the AACR Special Conference in Cancer Research: Cancer Evolution: The Dynamics of Progression and Persistence; 2025 Dec 4-6; Albuquerque, NM. Philadelphia (PA): AACR; Cancer Res 2025;85 (23Suppl): Abstract nr A012.

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