Autocrine INSL5 promotes tumor progression and glycolysis via activation of STAT5 signaling.
INSL5
STAT5
diagnosis
glycolysis
nasopharyngeal carcinoma
Journal
EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: England
ID NLM: 101487380
Informations de publication
Date de publication:
07 09 2020
07 09 2020
Historique:
received:
18
01
2020
revised:
15
06
2020
accepted:
18
06
2020
pubmed:
14
7
2020
medline:
19
8
2021
entrez:
14
7
2020
Statut:
ppublish
Résumé
Metabolic reprogramming plays important roles in development and progression of nasopharyngeal carcinoma (NPC), but the underlying mechanism has not been completely defined. In this work, we found INSL5 was elevated in NPC tumor tissue and the plasma of NPC patients. Plasma INSL5 could serve as a novel diagnostic marker for NPC, especially for serum VCA-IgA-negative patients. Moreover, higher plasma INSL5 level was associated with poor disease outcome. Functionally, INSL5 overexpression increased, whereas knockdown of its receptor GPCR142 or inhibition of INSL5 reduced cell proliferation, colony formation, and cell invasion in vitro and tumorigenicity in vivo. Mechanistically, INSL5 enhanced phosphorylation and nuclear translocation of STAT5 and promoted glycolytic gene expression, leading to induced glycolysis in cancer cells. Pharmaceutical inhibition of glycolysis by 2-DG or blockade of INSL5 by a neutralizing antibody reversed INSL5-induced proliferation and invasion, indicating that INSL5 can be a potential therapeutic target in NPC. In conclusion, INSL5 enhances NPC progression by regulating cancer cell metabolic reprogramming and is a potential diagnostic and prognostic marker as well as a therapeutic target for NPC.
Identifiants
pubmed: 32657028
doi: 10.15252/emmm.202012050
pmc: PMC7507000
doi:
Substances chimiques
STAT5 Transcription Factor
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12050Subventions
Organisme : National Key Research and Development Program of China
ID : 2017YFC0908503
Pays : International
Organisme : National Key Research and Development Program of China
ID : 2017YFA0505600
Pays : International
Organisme : National Key Research and Development Program of China
ID : 2016YFA0502101
Pays : International
Organisme : National Natural Science Foundation of China (NSF)
ID : 81830090
Pays : International
Organisme : National Natural Science Foundation of China (NSF)
ID : 81520108022
Pays : International
Organisme : National Natural Science Foundation of China (NSF)
ID : 81621004
Pays : International
Organisme : National Natural Science Foundation of China (NSF)
ID : 81802775
Pays : International
Organisme : National Natural Science Foundation of China (NSF)
ID : 81672703
Pays : International
Organisme : National Natural Science Foundation of China (NSF)
ID : 81772883
Pays : International
Organisme : Natural Science Foundation of Guang Dong Province
ID : 2017A030312003
Pays : International
Organisme : Guang Dong Province Key Research and Development Program
ID : 2019B020226002
Pays : International
Organisme : the Guangzhou Science Technology and Innovation Commission
ID : 201607020038
Pays : International
Organisme : China Postdoctoral Science Foundation
ID : 2019M663252
Pays : International
Informations de copyright
© 2020 The Authors. Published under the terms of the CC BY 4.0 license.
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