Keratin 18 induces proliferation, migration, and invasion in gastric cancer via the MAPK signalling pathway.

KRT18 MAPK gastric cancer malignant behaviour prognosis

Journal

Clinical and experimental pharmacology & physiology
ISSN: 1440-1681
Titre abrégé: Clin Exp Pharmacol Physiol
Pays: Australia
ID NLM: 0425076

Informations de publication

Date de publication:
Jan 2021
Historique:
revised: 01 08 2020
received: 11 04 2020
accepted: 12 08 2020
medline: 30 8 2020
pubmed: 30 8 2020
entrez: 30 8 2020
Statut: ppublish

Résumé

Keratin 18 (KRT18) is a cytoskeleton protein that plays a key role in multiple cancers. The present study aims to further investigate the roles of KRT18 in gastric cancer (GC) tissues and cells. The KRT18 protein expression levels of GC tissues and cells were detected using immunohistochemistry and western blot. The relationship between KRT18 expression levels and the prognosis of GC patients was further analyzed. To explore this relationship, small interfering RNA (siRNA) was used to inhibit the endogenous expression of KRT18 in GC cells. Furthermore, the effects of KRT18 on the proliferation, invasion, migration, and apoptosis of GC cells were analyzed in vitro. In addition, the role of KRT18 in GC-specific processes was investigated. Keratin 18 expression was shown to be up-regulated in GC tissues and associated with poor prognosis. Following KRT18 silencing with siRNA, the proliferation, invasion, and migration ability of GC cells were significantly inhibited, while the apoptotic process was promoted. Furthermore, the activation of the MAPK signalling pathway was identified as the potential mechanism through which KRT18 influenced GC processes. Keratin 18 plays a cancer-promoting role and might be a potential therapeutic target in the treatment of GC.

Identifiants

pubmed: 32860257
doi: 10.1111/1440-1681.13401
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

147-156

Informations de copyright

© 2020 John Wiley & Sons Australia, Ltd.

Références

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424.
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87-108.
Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66(2):115-132.
Zong L, Abe M, Seto Y, Ji J. The challenge of screening for early gastric cancer in China. Lancet. 2016;388(10060):2606.
Vatsalya V, Cave MC, Kong M, et al. Keratin 18 is a diagnostic and prognostic factor for acute alcoholic hepatitis. Clin Gastroenterol Hepatol. 2019;18(9):2046-2054.
Toivola DM, Nakamichi SP, et al. Keratin overexpression levels correlate with the extent of spontaneous pancreatic injury. Am J Pathol. 2008;172(4):882-892.
Sugimoto M, Inoko A, Shiromizu T, et al. The keratin-binding protein Albatross regulates polarization of epithelial cells. J Cell Biol. 2008;183(1):19-28.
Caulin C, Ware CF, Magin TM, Oshima RG. Keratin-dependent, epithelial resistance to tumor necrosis factor-induced apoptosis. J Cell Biol. 2000;149(1):17-22.
Kim S, Wong P, Coulombe PA. A keratin cytoskeletal protein regulates protein synthesis and epithelial cell growth. Nature. 2006;441(7091):362-365.
Pankov R, Umezawa A, Maki R, Der CJ, Hauser CA, Oshima RG. Oncogene activation of human keratin 18 transcription via the Ras signal transduction pathway. Proc Natl Acad Sci USA. 1994;91(3):873-877.
Oyama K, Fushida S, Kinoshita J, et al. Serum cytokeratin 18 as a biomarker for gastric cancer. Clin Exp Med. 2013;13(4):289-295.
Peduk S, Tatar C, Dincer M, et al. The role of serum CK18, TIMP1, and MMP-9 levels in predicting R0 resection in patients with gastric cancer. Dis Markers. 2018;2018:e5604702.
Lebherzeichinger D, Krenn CG, Roth GA. Keratin 18 and heat-shock protein in chronic kidney disease. Adv Clin Chem. 2013;62:123-149.
Koehler DR, Vicky H, Rosetta B, et al. Targeting transgene expression for cystic fibrosis gene therapy. Mol Ther. 2001;4(1):58-65.
Lai YCC, Cheng CC, Lai YS, et al. Cytokeratin 18-associated histone 3 modulation in hepatocellular carcinoma: a mini review. Cancer Genomics Proteomics. 2017;14(4):219-223.
Fortier AM, Asselin E, Cadrin M. Keratin 8 and 18 loss in epithelial cancer cells increases collective cell migration and cisplatin sensitivity through Claudin1 up-regulation. J Biol Chem. 2013;288(16):11555-11571.
Buchegger K, Silva R, López J, et al. The ERK/MAPK pathway is overexpressed and activated in gallbladder cancer. Pathol Res Pract. 2017;213(5):476-482.
Ahronian LG, Sennott EM, Van Allen EM, et al. Clinical acquired resistance to RAF inhibitor combinations in BRAF-mutant colorectal cancer through MAPK pathway alterations. Cancer Discov. 2015;5(4):358-367.

Auteurs

Peng-Bin Wang (PB)

Department of Gastroenterology, Lanzhou Second People's Hospital, Lanzhou, China.

Yan Chen (Y)

Department of Gastroenterology, Characteristic Medical Center of Strategic Support Army, Beijing, China.

Guang-Rong Ding (GR)

Department of Gastroenterology, Lanzhou Second People's Hospital, Lanzhou, China.

Hong-Wei Du (HW)

Department of Gastroenterology, Lanzhou Second People's Hospital, Lanzhou, China.

Hong-Yan Fan (HY)

Department of Gastroenterology, Lanzhou Second People's Hospital, Lanzhou, China.

Classifications MeSH