Oncogenic role of TYRO3 receptor tyrosine kinase in the progression of pancreatic cancer.
Aged
Animals
Carcinogenesis
Cell Line, Tumor
Cell Proliferation
Disease Progression
Female
Gene Knockdown Techniques
Humans
Kaplan-Meier Estimate
MAP Kinase Signaling System
Male
Mice
Middle Aged
Neoplasm Invasiveness
/ pathology
Neoplasm Staging
Pancreas
/ pathology
Pancreatic Neoplasms
/ mortality
Phosphorylation
Prognosis
Proto-Oncogene Proteins c-akt
/ metabolism
RNA, Small Interfering
/ metabolism
Receptor Protein-Tyrosine Kinases
/ genetics
Xenograft Model Antitumor Assays
Akt
ERK
Invasion
Prognosis
Proliferation
TAM family
Journal
Cancer letters
ISSN: 1872-7980
Titre abrégé: Cancer Lett
Pays: Ireland
ID NLM: 7600053
Informations de publication
Date de publication:
01 02 2020
01 02 2020
Historique:
received:
06
07
2019
revised:
15
11
2019
accepted:
18
11
2019
pubmed:
26
11
2019
medline:
1
9
2020
entrez:
26
11
2019
Statut:
ppublish
Résumé
The expression and functions of TYRO3, a member of the TAM receptor tyrosine kinase family, in pancreatic cancer (PC) have not been specifically elucidated. In this study, we confirmed TYRO3 expression in five human PC cell lines (PANC-1, MIA PaCa-2, BxPC-3, AsPC-1, and PK-9) using Western blotting. TYRO3 silencing and overexpression studies have revealed that TYRO3 promotes cell proliferation and invasion in PC via phosphorylation of protein kinase B (Akt) and extracellular signal-regulated kinase (ERK). Using a mouse xenograft model, we showed that tumor growth was significantly suppressed in mice subcutaneously inoculated with TYRO3-knockdown PC cells compared with mice inoculated with control PC cells. Furthermore, TYRO3 expression was examined in PC tissues obtained from 106 patients who underwent pancreatic resection for invasive ductal carcinoma through immunohistochemical staining. TYRO3-positive patients had poor prognoses for overall survival and disease-specific survival compared with TYRO3-negative patients. Multivariate analysis revealed that TYRO3 expression is an independent prognostic factor for overall survival. Our study demonstrates the critical role of TYRO3 in PC progression through Akt and ERK activation and suggests TYRO3 as a novel promising target for therapeutic strategies against PC.
Identifiants
pubmed: 31765735
pii: S0304-3835(19)30583-X
doi: 10.1016/j.canlet.2019.11.028
pii:
doi:
Substances chimiques
RNA, Small Interfering
0
Receptor Protein-Tyrosine Kinases
EC 2.7.10.1
TYRO3 protein, human
EC 2.7.10.1
AKT1 protein, human
EC 2.7.11.1
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
149-160Informations de copyright
Copyright © 2019 Elsevier B.V. All rights reserved.