E-viri
Recenzirano
Odprti dostop
-
Todoric, Jelena; Antonucci, Laura; Di Caro, Giuseppe; Li, Ning; Wu, Xuefeng; Lytle, Nikki K.; Dhar, Debanjan; Banerjee, Sourav; Fagman, Johan B.; Browne, Cecille D.; Umemura, Atsushi; Valasek, Mark A.; Kessler, Hannes; Tarin, David; Goggins, Michael; Reya, Tannishtha; Diaz-Meco, Maria; Moscat, Jorge; Karin, Michael
Cancer cell, 12/2017, Letnik: 32, Številka: 6Journal Article
Despite expression of oncogenic KRAS, premalignant pancreatic intraepithelial neoplasia 1 (PanIN1) lesions rarely become fully malignant pancreatic ductal adenocarcinoma (PDAC). The molecular mechanisms through which established risk factors, such as chronic pancreatitis, acinar cell damage, and/or defective autophagy increase the likelihood of PDAC development are poorly understood. We show that accumulation of the autophagy substrate p62/SQSTM1 in stressed KrasG12D acinar cells is associated with PDAC development and maintenance of malignancy in human cells and mice. p62 accumulation promotes neoplastic progression by controlling the NRF2-mediated induction of MDM2, which acts through p53-dependent and -independent mechanisms to abrogate checkpoints that prevent conversion of differentiated acinar cells to proliferative ductal progenitors. MDM2 targeting may be useful for preventing PDAC development in high-risk individuals. Display omitted •IKKα-deficiency-induced p62 accumulation drives PDAC progression•MDM2 links the autophagy substrate p62 to neoplastic progression in the pancreas•A p62-NRF2-MDM2 module acts via p53-dependent and -independent mechanisms•A p62-NRF2-MDM2 module converts acinar cells into progenitor-like cells Todoric et al. demonstrate that pancreatitis-induced accumulation of the autophagy substrate p62/SQSTM1 in the context of oncogenic KRAS promotes progression to pancreatic ductal adenocarcinoma. This p62 function relies on NRF2-driven induction of MDM2 and both p53 dependent and independent activity of MDM2.
Avtor
Vnos na polico
Trajna povezava
- URL:
Faktor vpliva
Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Baze podatkov, v katerih je revija indeksirana
Ime baze podatkov | Področje | Leto |
---|
Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
---|
Vir: Osebne bibliografije
in: SICRIS
To gradivo vam je dostopno v celotnem besedilu. Če kljub temu želite naročiti gradivo, kliknite gumb Nadaljuj.