Mechanism of SHP2 inhibiting M2 TAM regulation of nasopharyngeal carcinoma invasion and metastasis through IL-6/STAT3 and PI3K/AKT pathways
Lin Lin
Zhong Shuo
Cao Jinling
Zhang Xiufang
Chen Jinnan
Abstract：Objective To elucidate the molecular mechanism by which tyrosine phosphatase SHP2 regulates macro-phage M2 polarization in the tumor microenvironment and its inhibitory effect on the invasion and metastasis of nasopharyn-geal carcinoma(NPC).Methods The experiment was conducted in the laboratory of the Medical Research Center of Kailuan General Hospital in June 2024.A lentiviral vector overexpressing SHP2 was constructed and used to infect THP-1 monocytes to establish a stable macrophage model overexpressing SHP2(SHP2-THP-1).Cells were divided into blank control group,THP-1 group,and SHP2-THP-1 group,and co-cultured with conditioned medium from NPC CNE-1 cells.Quantitative real-time PCR(qRT-PCR)and Western blot were used to detect the expression of M2 polarization markers(IL-10,Arg1,CD 163,CD206)and key proteins in the IL-6/STAT3 and PI3K/AKT signaling pathways.The effects of supernatants from each group on the migration and invasion abilities of CNE-1 cells were evaluated using wound healing and Transwell assays.Results Compared with the blank control group,the mRNA expression levels of M2 markers(IL-10,Arg1,CD163,CD206)in THP-1 cells treated with CNE-1 conditioned medium were significantly increased(P＜0.05).Compared with the THP-1 group,the SHP2 overexpression group(SHP2-THP-1)showed a significant decrease in the expression of these M2 markers(P＜0.05).Western blot analysis revealed that overexpression of SHP2 significantly inhibited the protein expression of IL-6,p-STAT3(Tyr705),p-PI3K,and p-AKT(Ser473)(P＜0.05).Functional assays demonstrated that the migration rate and invasion number of CNE-1 cells were significantly higher in the THP-1 supernatant group than in the blank control group(P＜0.05),whereas these parameters were significantly lower in the SHP2-THP-1 supernatant group compared with the THP-1 supernatant group(P＜0.05).Conclusion SHP2 inhibits tumor microenvironment-induced M2 polarization of macrophages by suppressing IL-6/STAT3 and PI3K/AKT signaling,thereby attenuating NPC cell invasion and metastasis.These findings highlight the therapeutic potential of targeting the SHP2-immunometabolic axis in NPC.
Keywords：Nasopharyngeal carcinomaInvasion and metastasisM2-polarized tumor-associated macrophagesSrc homology 2 domain-containing protein tyrosine phosphatase
Publication Date：2026-03-18
Online Publishing Date：2026-04-08(First online date of this platform, not the publication date of the document)
Pages：6( 353-358 )