Autocrine INSL5 promotes tumor progression and glycolysis via activation of STAT5 signaling

Autor: Shi‐Bing Li, Yan‐Yan Liu, Li Yuan, Ming‐Fang Ji, Ao Zhang, Hui‐Yu Li, Lin‐Quan Tang, Shuo‐Gui Fang, Hua Zhang, Shan Xing, Man‐Zhi Li, Qian Zhong, Shao‐Jun Lin, Wan‐Li Liu, Peng Huang, Yi‐Xin Zeng, Yu‐Ming Zheng, Zhi‐Qiang Ling, Jian‐Hua Sui, Mu‐Sheng Zeng
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: EMBO Molecular Medicine, Vol 12, Iss 9, Pp 1-19 (2020)
Druh dokumentu: article
ISSN: 1757-4676
1757-4684
DOI: 10.15252/emmm.202012050
Popis: Abstract 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.
Databáze: Directory of Open Access Journals
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