Ubiquitin signaling in pancreatic ductal adenocarcinoma

被引:2
|
作者
Lv, Shengnan [1 ]
Zhang, Jian [1 ]
Peng, Xinyu [1 ]
Liu, Huan [1 ]
Liu, Yan [2 ]
Wei, Feng [1 ]
机构
[1] First Hosp Jilin Univ, Gen Surg Ctr, Dept Hepatobiliary & Pancreat Surg, Changchun, Jilin, Peoples R China
[2] Chinese Acad Agr Sci, Changchun Vet Res Inst, Key Lab Jilin Prov Zoonosis Prevent & Control, Changchun, Peoples R China
基金
中国国家自然科学基金;
关键词
pancreatic ductal adenocarcinoma; ubiquitination; ubiquitin-protein ligases; deubiquitinating enzymes; proteolysis-targeting chimeras; CANCER PROGRESSION; ACHIEVES SAFE; BETA-CATENIN; PROMOTES; GROWTH; PROTAC; CHEMORESISTANCE; EXPRESSION; PROTEINS; PROLIFERATION;
D O I
10.3389/fmolb.2023.1304639
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignant tumor of the digestive system, characterized by rapid progression and being prone to metastasis. Few effective treatment options are available for PDAC, and its 5-year survival rate is less than 9%. Many cell biological and signaling events are involved in the development of PDAC, among which protein post-translational modifications (PTMs), such as ubiquitination, play crucial roles. Catalyzed mostly by a three-enzyme cascade, ubiquitination induces changes in protein activity mainly by altering their stability in PDAC. Due to their role in substrate recognition, E3 ubiquitin ligases (E3s) dictate the outcome of the modification. Ubiquitination can be reversed by deubiquitylases (DUBs), which, in return, modified proteins to their native form. Dysregulation of E3s or DUBs that disrupt protein homeostasis is involved in PDAC. Moreover, the ubiquitination system has been exploited to develop therapeutic strategies, such as proteolysis-targeting chimeras (PROTACs). In this review, we summarize recent progress in our understanding of the role of ubiquitination in the development of PDAC and offer perspectives in the design of new therapies against this highly challenging disease.
引用
收藏
页数:17
相关论文
共 50 条
  • [31] Hypoxia and pancreatic ductal adenocarcinoma
    Yamasaki, Akio
    Yanai, Kosuke
    Onishi, Hideya
    CANCER LETTERS, 2020, 484 : 9 - 15
  • [32] Macrophages and pancreatic ductal adenocarcinoma
    Habtezion, Aida
    Edderkaoui, Mouad
    Pandol, Stephen J.
    CANCER LETTERS, 2016, 381 (01) : 211 - 216
  • [33] Staging of pancreatic ductal adenocarcinoma
    Sauvanet, A
    Zins, M
    JOURNAL DE CHIRURGIE, 1998, 135 (01): : 10 - 16
  • [34] FOLFIRINOX for Pancreatic Ductal Adenocarcinoma
    Alakus, Hakan
    Korenkov, Michael
    Kuetting, Fabian
    Bruns, Christiane
    ONKOLOGE, 2019, 25 (08): : 726 - 727
  • [35] Immunotherapy for pancreatic ductal adenocarcinoma
    Carpenter, Eileen
    Nelson, Sarah
    Bednar, Filip
    Cho, Clifford
    Nathan, Hari
    Sahai, Vaibhav
    di Magliano, Marina Pasca
    Frankel, Timothy L.
    JOURNAL OF SURGICAL ONCOLOGY, 2021, 123 (03) : 751 - 759
  • [36] Biomarkers in pancreatic ductal adenocarcinoma
    Gallego, J.
    Lopez, C.
    Pazo-Cid, R.
    Lopez-Rios, F.
    Carrato, A.
    CLINICAL & TRANSLATIONAL ONCOLOGY, 2017, 19 (12): : 1430 - 1437
  • [37] Desmoplasia of Pancreatic Ductal Adenocarcinoma
    Pandol, Stephen
    Edderkaoui, Mouad
    Gukovsky, Ilya
    Lugea, Aurelia
    Gukovskaya, Anna
    CLINICAL GASTROENTEROLOGY AND HEPATOLOGY, 2009, 7 (11) : S44 - S47
  • [38] Models of pancreatic ductal adenocarcinoma
    Rayane Dennaoui
    Hridaya Shrestha
    Kay-Uwe Wagner
    Cancer and Metastasis Reviews, 2021, 40 : 803 - 818
  • [39] Carcinogenesis of Pancreatic Ductal Adenocarcinoma
    Storz, Peter
    Crawford, Howard C.
    GASTROENTEROLOGY, 2020, 158 (08) : 2072 - 2081
  • [40] Genomics of pancreatic ductal adenocarcinoma
    Pilarsky, Christian
    Gruetzmann, Robert
    HEPATOBILIARY & PANCREATIC DISEASES INTERNATIONAL, 2014, 13 (04) : 381 - 385