The glycoprotein CD44 is a transmembrane receptor which has been connected to multiple biological processes, specifically to cancer cells stemness, angiogenesis and epithelial mesenchymal transition. Hyaluronic acid is the main CD44 ligand and studies have demonstrated its involvement in regulation of tumour progression. CD44-HA axis has been recently identified as a major player in iron homeostasis and epigenetic regulation in cancer cells. Moreover, CD44 interaction with the deubiquitinating enzyme OTUB1 mediates the stabilisation of a subunit of the Cystine-Glutamate antiporter Xc, SLC7A11, leading to increased ferroptosis resistance in cancer cells. Since their pivotal role in modulating cancer cell mobility and susceptibility to iron induced cell death, CD44 and HA can be targeted in cancer therapy; indeed, oxidative insults, that can result from chemotherapy, directly hinder CD44-HA interaction decreasing cancer cell proliferation and viability. Thus, by enlightening the complex and pleiotropic role of CD44-HA axis in cancer cell it might be possible to pin point new treatable targets for tumour cells resistant to classic cancer therapy approaches.
The glycoprotein CD44 is a transmembrane receptor which has been connected to multiple biological processes, specifically to cancer cells stemness, angiogenesis and epithelial mesenchymal transition. Hyaluronic acid is the main CD44 ligand and studies have demonstrated its involvement in regulation of tumour progression. CD44-HA axis has been recently identified as a major player in iron homeostasis and epigenetic regulation in cancer cells. Moreover, CD44 interaction with the deubiquitinating enzyme OTUB1 mediates the stabilisation of a subunit of the Cystine-Glutamate antiporter Xc, SLC7A11, leading to increased ferroptosis resistance in cancer cells. Since their pivotal role in modulating cancer cell mobility and susceptibility to iron induced cell death, CD44 and HA can be targeted in cancer therapy; indeed, oxidative insults, that can result from chemotherapy, directly hinder CD44-HA interaction decreasing cancer cell proliferation and viability. Thus, by enlightening the complex and pleiotropic role of CD44-HA axis in cancer cell it might be possible to pin point new treatable targets for tumour cells resistant to classic cancer therapy approaches.
CD44 and Hyaluronic acid: the new door to target cancer cell iron metabolism
SIVIERO, FRANCESCA
2020/2021
Abstract
The glycoprotein CD44 is a transmembrane receptor which has been connected to multiple biological processes, specifically to cancer cells stemness, angiogenesis and epithelial mesenchymal transition. Hyaluronic acid is the main CD44 ligand and studies have demonstrated its involvement in regulation of tumour progression. CD44-HA axis has been recently identified as a major player in iron homeostasis and epigenetic regulation in cancer cells. Moreover, CD44 interaction with the deubiquitinating enzyme OTUB1 mediates the stabilisation of a subunit of the Cystine-Glutamate antiporter Xc, SLC7A11, leading to increased ferroptosis resistance in cancer cells. Since their pivotal role in modulating cancer cell mobility and susceptibility to iron induced cell death, CD44 and HA can be targeted in cancer therapy; indeed, oxidative insults, that can result from chemotherapy, directly hinder CD44-HA interaction decreasing cancer cell proliferation and viability. Thus, by enlightening the complex and pleiotropic role of CD44-HA axis in cancer cell it might be possible to pin point new treatable targets for tumour cells resistant to classic cancer therapy approaches.| File | Dimensione | Formato | |
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Descrizione: CD44 and Hyaluronic acid: the new door to target cancer cell iron metabolism
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https://hdl.handle.net/20.500.14240/2966