Open AccessAutocrine INSL 5 promotes tumor progression and glycolysis via activation of STAT 5 signaling
Author(s) -
Li ShiBing,
Liu YanYan,
Yuan Li,
Ji MingFang,
Zhang Ao,
Li HuiYu,
Tang LinQuan,
Fang ShuoGui,
Zhang Hua,
Xing Shan,
Li ManZhi,
Zhong Qian,
Lin ShaoJun,
Liu WanLi,
Huang Peng,
Zeng YiXin,
Zheng YuMing,
Ling ZhiQiang,
Sui JianHua,
Zeng MuSheng
Publication year - 2020
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.202012050
Subject(s) - stat , autocrine signalling , glycolysis , chemistry , signal transduction , microbiology and biotechnology , biochemistry , biology , receptor , metabolism , stat3
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 INSL 5 was elevated in NPC tumor tissue and the plasma of NPC patients. Plasma INSL 5 could serve as a novel diagnostic marker for NPC , especially for serum VCA ‐IgA‐negative patients. Moreover, higher plasma INSL 5 level was associated with poor disease outcome. Functionally, INSL 5 overexpression increased, whereas knockdown of its receptor GPCR 142 or inhibition of INSL 5 reduced cell proliferation, colony formation, and cell invasion in vitro and tumorigenicity in vivo . Mechanistically, INSL 5 enhanced phosphorylation and nuclear translocation of STAT 5 and promoted glycolytic gene expression, leading to induced glycolysis in cancer cells. Pharmaceutical inhibition of glycolysis by 2‐ DG or blockade of INSL 5 by a neutralizing antibody reversed INSL 5‐induced proliferation and invasion, indicating that INSL 5 can be a potential therapeutic target in NPC . In conclusion, INSL 5 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 .