2. Academic Validation
  3. Glycocalyx hyaluronan removal-induced increasing of cell stiffness delays breast cancer cells progression

Glycocalyx hyaluronan removal-induced increasing of cell stiffness delays breast cancer cells progression

  • Cell Mol Life Sci. 2025 Feb 27;82(1):96. doi: 10.1007/s00018-025-05577-0.
Hui Wang # 1 2,  Guoliang Zhang # 1,  Yiwen Liu 1,  Yiqing He 1,  Qian Guo 1,  Yan Du 1,  Cuixia Yang 1 2,  Feng Gao 3 4
Affiliations

Affiliations

  • 1 Department of Molecular Biology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, 600 Yishan Road, Shanghai, 200233, China.
  • 2 Department of Clinical Laboratory, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, 600 Yishan Road, Shanghai, 200233, China.
  • 3 Department of Molecular Biology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, 600 Yishan Road, Shanghai, 200233, China. gaofengly@sjtu.edu.cn.
  • 4 Department of Clinical Laboratory, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, 600 Yishan Road, Shanghai, 200233, China. gaofengly@sjtu.edu.cn.
  • # Contributed equally.
PMID: 40011237 DOI: 10.1007/s00018-025-05577-0
Abstract

Triple-negative breast Cancer (TNBC) cells are rich in glycocalyx (GCX) that is closely correlated with the reorganization of cytoskeletal filaments. Most studies have focused on cell membrane glycoproteins in this context, but rarely on the significance of glycosaminoglycans, particularly the hyaluronan (HA)-associated GCX. Here, we reported that removal of GCX HA could significantly increase breast Cancer cells (BCCs) stiffness, leading to impaired cell growth and decreased stem-like properties. Furthermore, we found that the delay of TNBC cells progression could be restored after the cells were re-softened. Meanwhile, in vivo studies revealed that hyaluronidase (HAase)-pretreated BCCs displayed reduced tumor growth and migration. Intriguingly, we identified that ZC3H12A, a zinc-finger RNA binding protein encoded gene, was significantly upregulated after the GCX HA impairment. Of note, knockdown of ZC3H12A could soften the HAase-treated TNBC cells, implying a GCX HA-ZC3H12A regulation on cell stiffening. Taken together, our findings suggested that the breakdown of pericellular HA coat could influence TNBC cells mechanical properties which might be helpful to the future breast Cancer research.

Keywords

Cell progression; Cell stiffness; Glycocalyx; Hyaluronan; ZC3H12A.

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