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  1. Philip J Smith
  1. Department of Gastroenterology, Royal Liverpool Hospital, Liverpool University Hospitals NHS Foundation Trust, Liverpool, L7 8XP, UK
  1. Correspondence to Dr Philip J Smith, Department of Gastroenterology, Royal Liverpool Hospital, Liverpool University Hospitals NHS Foundation Trust, Liverpool, L7 8XP, UK; Philip.Smith{at}liverpoolft.nhs.uk

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Basic science

Tumours demonstrate a potential new ‘Achilles’ heel’ of fibrosis

Ros M, Nguyen A, Chia J, et al. ER-resident oxidoreductases are glycosylated and trafficked to the cell surface to promote matrix degradation by tumour cells. Nat Cell Biol 2020; 22:1371–81. doi: 10.1038/s41556-020-00590-w.

Fibrosis is a heterogeneous amalgum of extracellular matrix (ECM) proteins which can be remodelled and degraded by protein digesting proteases. Crosslinked fibrosis is resistant to protease degradation and understanding how crosslinks form may offer many novel forms of therapy. Fibrosis is responsible for many diseases but fibrous boundaries of tumours may also prevent their growth and spread. Breaking down fibrosis, allowing invasion and metastasis, is a hallmark of cancer. In this study the researchers studied the glycosylation of the calnexin protein. They identified this as a target of a pathway known to be active in both cancer and specialised cells (eg, osteoclasts) which share the use of specialised structures to degrade tissue. The researchers showed that glycosylated calnexin was present in both liver and other tumours and, by detecting the release of gelatin accessed through an ECM covering, that it degraded fibrosis. As calnexin plays a role in protein isomerisation of disulphide bonds within cells the researchers then studied whether disulphide bonds crosslink the ECM. They showed that liver ECM is rich is disulphide bonds which can be broken down by glutathione catalysed by glycosylated calnexin. In cancer assays, including liver tumours, inhibition of calnexin prevented tumour metastasis and slowed primary tumour growth. Targeting this process may therefore provide a means to treat many forms of cancer. Likewise, this process may also be a target for treating fibrosis in cirrhosis and other fibrotic diseases.

Shining a LIGHT on the pathogenesis of eosinophilic oesophagitis

Manresa M, Chiang A, Kurten R, et al. Increased production of LIGHT by T cells in eosinophilic esophagitis promotes differentiation of esophageal fibroblasts toward an inflammatory phenotype. Gastroenterology 2020; 159:1778–92.

Eosinophilic oesophagitis …

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Footnotes

  • Funding The author has not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

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