Liprin-α4 as a New Therapeutic Target for SCLC as an Upstream Mediator of HIF1α.
Antineoplastic Agents
/ pharmacology
Cell Line, Tumor
Cisplatin
/ pharmacology
Humans
Hypoxia-Inducible Factor 1, alpha Subunit
/ genetics
Lung Neoplasms
/ genetics
RNA, Small Interfering
/ administration & dosage
Receptor-Like Protein Tyrosine Phosphatases
/ genetics
Small Cell Lung Carcinoma
/ genetics
HIF1α
Liprin-α4
SCLC
invasion
proliferation
Journal
Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988
Informations de publication
Date de publication:
Mar 2019
Mar 2019
Historique:
received:
03
01
2019
revised:
01
02
2019
accepted:
04
02
2019
entrez:
8
3
2019
pubmed:
8
3
2019
medline:
12
3
2019
Statut:
ppublish
Résumé
Small-cell lung cancer (SCLC) remains one of deadliest types of cancers. Cis-diamminedichloroplatinum (CDDP) is a key chemotherapeutic agent for SCLC, however, its therapeutic effect is limited. Recently, hypoxia in the cancer microenvironment has been suggested to influence the effect of cancer therapy. Using small interfering RNA inhibition of leukocyte common antigen-related interacting protein alpha 4 (liprin-α4), and of hypoxia-inducible factor (HIF)-1α, proliferation, invasion, migration and chemosensitivity were investigated in SBC-5 SCLC cells, under normoxia and hypoxia. Liprin-α4 was found to contribute to proliferation, but not migration and invasion of SBC-5 cells both under normoxia and hypoxia. Inhibition of liprin-α4 increased chemosensitivity of SBC-5 cells under hypoxia. Liprin-α4 signaling occurs through mitogen-activated protein kinase pathways via activation of HIF1α expression. Inhibition of HIF1α reduced proliferation and increased chemosensitivity of SBC-5 cells under hypoxia. Liprin-α4 inhibition may enhance the effect of CDDP and liprin-α4 might be a novel therapeutic target in SCLC.
Sections du résumé
BACKGROUND/AIM
OBJECTIVE
Small-cell lung cancer (SCLC) remains one of deadliest types of cancers. Cis-diamminedichloroplatinum (CDDP) is a key chemotherapeutic agent for SCLC, however, its therapeutic effect is limited. Recently, hypoxia in the cancer microenvironment has been suggested to influence the effect of cancer therapy.
MATERIALS AND METHODS
METHODS
Using small interfering RNA inhibition of leukocyte common antigen-related interacting protein alpha 4 (liprin-α4), and of hypoxia-inducible factor (HIF)-1α, proliferation, invasion, migration and chemosensitivity were investigated in SBC-5 SCLC cells, under normoxia and hypoxia.
RESULTS
RESULTS
Liprin-α4 was found to contribute to proliferation, but not migration and invasion of SBC-5 cells both under normoxia and hypoxia. Inhibition of liprin-α4 increased chemosensitivity of SBC-5 cells under hypoxia. Liprin-α4 signaling occurs through mitogen-activated protein kinase pathways via activation of HIF1α expression. Inhibition of HIF1α reduced proliferation and increased chemosensitivity of SBC-5 cells under hypoxia.
CONCLUSION
CONCLUSIONS
Liprin-α4 inhibition may enhance the effect of CDDP and liprin-α4 might be a novel therapeutic target in SCLC.
Identifiants
pubmed: 30842147
pii: 39/3/1179
doi: 10.21873/anticanres.13227
doi:
Substances chimiques
Antineoplastic Agents
0
Hypoxia-Inducible Factor 1, alpha Subunit
0
RNA, Small Interfering
0
PPFIA4 protein, human
EC 3.1.3.48
Receptor-Like Protein Tyrosine Phosphatases
EC 3.1.3.48
Cisplatin
Q20Q21Q62J
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1179-1184Informations de copyright
Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.