Id2 regulates the metabolic reprogramming of Tcm cells through the PI3K/AKT pathway to inhibit colorectal cancer cell growth
10.3872/j.issn.1007-385x.2025.06.002
- VernacularTitle:Id2通过PI3K/AKT通路调控Tcm细胞的代谢重编程抑制结肠癌细胞生长
- Author:
Fang LIU
1
;
Chunli PAN
;
Zhifeng ZHOU
;
Shuping CHEN
;
Yunbin YE
Author Information
1. 福建医科大学肿瘤临床医学院,福建省肿瘤医院 肿瘤免疫学研究室,福建 福州 350014;福建医科大学 基础医学院,福建 福州 350122;福建省肿瘤转化医学重点实验室,福建 福州 350014
- Publication Type:Journal Article
- Keywords:
inhibitor of differentiation 2(Id2);
central memory T(Tcm)cell;
T cell differentiation;
PI3K/AKT signal pathway;
metabolic reprogramming
- From:
Chinese Journal of Cancer Biotherapy
2025;32(6):570-578
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the role of inhibitor of differentiation 2(Id2)in inducing the generation of central memory T(Tcm)cells and enhancing the anti-tumor persistence of T cells.Methods:CD8+na?ve T cells were sorted with magnetic beads and then co-cultured with carcinoembryonic antigen(CEA)-loaded dendritic cells(DCs).These cells were induced into effector T(Teff)or Tcm cells by interleukin-2(IL-2)or IL-7/15/21/23,respectively.The mRNA and protein expression of Id2 and Id3 in T cells were detected using qPCR and WB,respectively.Id2 gene in T cells was knocked down using lentivirus,and the T cell memory phenotype was analyzed by flow cytometry.The expression of PI3K/AKT pathway-related proteins was examined by WB.The extracellular acidification rate(ECAR)and oxygen consumption rate(OCR)were assessed using a Seahorse extracellular flux analyzer.A zebrafish colorectal cancer HCT116 xenograft model was employed to analyze the anti-tumor differences between Teff and Tcm cells.The effect of Id2 gene knockdown in Tcm cells(Tcm-shId2)on the growth inhibition of secondary xenografts was also observed.Results:Tcm cells exhibited high expression of Id3 mRNA(P<0.05),whereas Teff cells showed high expression of Id2 mRNA(P<0.001).Tcm cells with Id2 knockdown(Tcm-shId2)were successfully constructed,showing significantly upregulated Id3 expression.Knockdown of Id2 promoted the formation of Tcm cell(P<0.05).Tcm-shId2 cells underwent metabolic reprogramming via the PI3K/AKT pathway,which effectively suppressed the growth of colorectal cancer xenografts in zebrafish and also produced significant inhibitory effects on secondary tumor growth(P<0.01).Conclusion:Id2 gene may regulate T cell metabolism through the PI3K/AKT signaling pathway,promoting the differentiation of CD8+T cells into Tcm cells and effectively inhibiting the growth of colorectal cancer xenografts.
