Crabp2 Promotes Metastasis of Lung Cancer Cells via HuR and Integrin β1/FAK/ERK Signaling.
Adenocarcinoma
/ genetics
Animals
Anoikis
Cell Line, Tumor
Cell Movement
Cell Proliferation
ELAV-Like Protein 1
/ metabolism
Focal Adhesion Kinase 1
/ metabolism
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Humans
Lung Neoplasms
/ genetics
Lymph Nodes
/ pathology
Lymphatic Metastasis
MAP Kinase Signaling System
Mice
Mice, Inbred BALB C
Neoplasms, Experimental
Receptors, Retinoic Acid
/ genetics
Up-Regulation
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
29 01 2019
29 01 2019
Historique:
received:
18
06
2018
accepted:
30
11
2018
entrez:
31
1
2019
pubmed:
31
1
2019
medline:
5
9
2020
Statut:
epublish
Résumé
Increased Crabp2 levels have been found in various types of cancer, and are associated with poor patients' survival. Although Crabp2 is found to be overexpressed in lung cancer, its role in metastasis of lung cancer is unclear. In this study, Crabp2 was overexpressed in high-metastatic C10F4 than low-metastatic lung cancer cells. Analysis of clinical samples revealed that high CRABP2 levels were correlated with lymph node metastases, poor overall survival, and increased recurrence. Knockdown of Crabp2 decreased migration, invasion, anoikis resistance, and in vivo metastasis. Crabp2 was co-immunoprecipitated with HuR, and overexpression of Crabp2 increased HuR levels, which promoted integrin β1/FAK/ERK signaling. Inhibition of HuR or integrin β1/FAK/ERK signaling reversed the promoting effect of Crabp2 in migration, invasion, and anoikis resistance. Knockdown of Crabp2 further inhibited the growth of cancer cells as compared with that by gemcitabine or irinotecan alone. The expression of Crabp2 in human lung tumors was correlated with stress marker CHOP. In conclusion, our findings have identified the promoting role of Crabp2 in anoikis resistance and metastasis. CRABP2 may serve as a prognostic marker and targeting CRABP2 may be exploited as a modality to reduce metastasis.
Identifiants
pubmed: 30696915
doi: 10.1038/s41598-018-37443-4
pii: 10.1038/s41598-018-37443-4
pmc: PMC6351595
doi:
Substances chimiques
ELAV-Like Protein 1
0
Receptors, Retinoic Acid
0
retinoic acid binding protein II, cellular
0
Focal Adhesion Kinase 1
EC 2.7.10.2
PTK2 protein, human
EC 2.7.10.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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