Endoplasmic reticulum stress, unfolded protein response and development of colon adenocarcinoma.
When misfolded proteins accumulate in the endoplasmic reticulum (ER), the cell is said to experience ER stress. This triggers an unfolded protein response (UPR) to restore the balance between misfolded proteins and ER chaperones such as BiP. UPR signalling is required for the growth of many solid ca...
| Publicado en: | Virchows Archiv: European Journal of Pathology Vol. 469; no. 2; pp. 145 - 155 |
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| Autores principales: | , , , , , , , |
| Formato: | Journal Article |
| Publicado: |
Springer Nature
Aug2016
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=117321330&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 117321330 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 09456317 O1Z jtl: Virchows Archiv: European Journal of Pathology issn: 09456317 maglogo: N pubinfo: dt: Aug2016 vid: 469 iid: 2 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 117321330 117321330 NLM27220766 10.1007/s00428-016-1961-6 NLM27220766 117321330 ppf: 145 ppct: 10 formats: fmt: @attributes: type: P tig: atl: Endoplasmic reticulum stress, unfolded protein response and development of colon adenocarcinoma. aug: au: Piton, Nicolas Wason, James Colasse, Élodie Cornic, Marie Lemoine, Françoise Le Pessot, Florence Marguet, Florent Sabourin, Jean-Christophe Colasse, Élodie Lemoine, Françoise affil: Department of Pathology , Rouen University Hospital , Rouen France sug: subj: Colonic Neoplasms Metabolism Proteins Physiology Cytoplasm Metabolism Middle Age Colonic Neoplasms Pathology Aged Transcription Factors Aged, 80 and Over Adenocarcinoma Metabolism DNA-Binding Proteins Male Adult Middle Aged: 45-64 years Aged: 65+ years Aged, 80 & over Adult: 19-44 years Male ab: When misfolded proteins accumulate in the endoplasmic reticulum (ER), the cell is said to experience ER stress. This triggers an unfolded protein response (UPR) to restore the balance between misfolded proteins and ER chaperones such as BiP. UPR signalling is required for the growth of many solid cancers. In chronic ER stress, factors including CHOP have been shown to mediate cell death. Colorectal adenocarcinoma arises due to progressive changes within pre-malignant lesions. Our aim was to test the hypothesis that the expression of BiP and CHOP correlates with the progression of those pre-malignant lesions.Eighty-one patients with colon neoplasms treated at Rouen University Hospital between January 1, 2003 and January 1, 2013 were randomly selected. The expression of BiP and CHOP was estimated by immunohistochemical staining of a tissue microarray generated from colon cores: normal tissue, low-grade and high-grade adenoma, invasive colon adenocarcinoma and lymph node metastasis of colon adenocarcinoma. In parallel, nine cases comprising areas from normal epithelium to dyplasia to invasive carcinoma and included in the TMA were analysed on whole sections.As colon epithelium shows increasing evidence of pre-malignant and then malignant changes, BiP expression significantly increases (p for trend < 0.001), whereas CHOP expression is attenuated (p for trend < 0.001).We identified a positive relationship between BiP expression and colon carcinogenesis, and a negative correlation for CHOP expression. These findings are consistent with a model in which ER stress accompanies oncogenesis and in which loss of proteins that mediate the toxicity of ER stress, such as CHOP, may facilitate tumorigenesis. This raises the exciting possibility that restoration of the negative feedback loop of UPR, if achievable, might antagonise the malignant process. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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