Journal Article Review Epublish
PubMed: 40507943 DOI: 10.3390/ijms26115132
Hyaluronan: An Architect and Integrator for Cancer and Neural Diseases.
Int J Mol Sci 26(11)
Authors: Che-Yu Hsu, Hieu-Huy Nguyen-Tran, Yu-An Chen, Kuan-Ting Lee, Tzong-Yuan Juang, Ming-Fu Chiang, Shin-Yi Liu, Nan-Shan Chang
Affiliations
- Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
- Graduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung 40402, Taiwan.
- Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei 10617, Taiwan .
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
- Department of Cosmeceutics, China Medical University, Taichung 40402, Taiwan.
- Department of Neurosurgery, Fu Jen Catholic University Hospital, Taipei 24352, Taiwan.
- Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung 40402, Taiwan.
- Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, New York, NY 10314, USA.
Abstract
Hyaluronan (HA) is essentially secreted by every cell and plays a critical role in maintaining normal cell physiology. While the structure and function of HA have been extensively investigated, questions regarding the sizes and conformation of HA under physiological and inflamed conditions, in relevance to its functions, remain elusive. In this article, we update our knowledge of the HA functional properties, including binding proteins and their signaling networks, as well as matrix formation, which can potentially induce phase separation and affect the mobility and behavior of small molecules, proteins, and cells. We detail the striking differences regarding the biological outcomes of signaling pathways for HA and membrane receptors versus HA and GPI-linked hyaluronidase Hyal-2. We describe: (1) the native, large-sized HA is not proapoptotic but signals with an overexpressed HYAL-2/WWOX/SMAD4 complex to induce apoptosis, which is likely to occur in an inflamed microenvironment; (2) HA-binding proteins are connected via signal pathway networks. The competitive binding of HA and TGF-β to the membrane HYAL-2 and the downstream HYAL-2/WWOX/SMAD4 signaling is addressed; (3) the phase-separated proteins or small molecules in the HA matrices may contribute to the aberrant interactions, leading to inflammation and disease progression; (4) the role of HA and complement C1q in Alzheimer's disease via connection with a risk factor for Alzheimer's disease WWOX is also discussed; (5) a hidden function is the inducible HA conformational changes that confer cancer suppression and, probably, retardation of neurodegeneration.
MeSH
Cells, Carrier Proteins, Neoplasms, Complement C1Q, Membranes, Small Molecules