Autocrine INSL 5 promotes tumor progression and glycolysis via activation of STAT 5 signaling

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 no...

Full description

Saved in:
Bibliographic Details
Published in:EMBO molecular medicine 2020-09, Vol.12 (9)
Main Authors: Li, Shi‐Bing, Liu, Yan‐Yan, Yuan, Li, Ji, Ming‐Fang, Zhang, Ao, Li, Hui‐Yu, Tang, Lin‐Quan, Fang, Shuo‐Gui, Zhang, Hua, Xing, Shan, Li, Man‐Zhi, Zhong, Qian, Lin, Shao‐Jun, Liu, Wan‐Li, Huang, Peng, Zeng, Yi‐Xin, Zheng, Yu‐Ming, Ling, Zhi‐Qiang, Sui, Jian‐Hua, Zeng, Mu‐Sheng
Format: Article
Language:English
Subjects:
Autocrine signalling
Biomarkers
Cancer
Cell growth
Cell proliferation
Gene expression
Glucose
Glycolysis
Homeostasis
Immunoglobulin A
Infections
Insulin
Medical prognosis
Metabolism
Nasopharyngeal carcinoma
Nuclear transport
Phosphorylation
Plasma
Proteins
Stat5 protein
Therapeutic applications
Throat cancer
Tumorigenicity
Tumors
Viruses
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1757-4676
1757-4684
DOI:10.15252/emmm.202012050