Dual roles of HK3 in regulating the network between tumor cells and tumor-associated macrophages in neuroblastoma

作者全名：Wu, Xin; Mi, Tao; Jin, Liming; Ren, Chunnian; Wang, Jinkui; Zhang, Zhaoxia; Liu, Jiayan; Wang, Zhaoyin; Guo, Peng; He, Dawei

作者地址：[Wu, Xin; Mi, Tao; Jin, Liming; Ren, Chunnian; Wang, Jinkui; Zhang, Zhaoxia; Liu, Jiayan; Wang, Zhaoyin; Guo, Peng; He, Dawei] Chongqing Med Univ, Childrens Hosp, Natl Clin Res Ctr Child Hlth & Disorders, Dept Urol,Minist Educ Key Lab Child Dev & Disorder, Chongqing 400014, Peoples R China; [Wu, Xin; Mi, Tao; Jin, Liming; Ren, Chunnian; Wang, Jinkui; Zhang, Zhaoxia; Liu, Jiayan; Wang, Zhaoyin; Guo, Peng; He, Dawei] Chongqing Key Lab Struct Birth Defect & Reconstruc, Chongqing 400014, Peoples R China; [Guo, Peng] Chinese Acad Sci, Inst Basic Med & Canc IBMC, Hangzhou 310022, Zhejiang, Peoples R China

通信作者：He, DW (通讯作者)，Chongqing Med Univ, Childrens Hosp, Natl Clin Res Ctr Child Hlth & Disorders, Dept Urol,Minist Educ Key Lab Child Dev & Disorder, Chongqing 400014, Peoples R China.; He, DW (通讯作者)，Chongqing Key Lab Struct Birth Defect & Reconstruc, Chongqing 400014, Peoples R China.

来源：CANCER IMMUNOLOGY IMMUNOTHERAPY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:001215470200002

JCR分区：Q1

影响因子：4.6

年份：2024

卷号：73

期号：7

开始页：　

结束页：　

文献类型：Article

关键词：HK3; Neuroblastoma; M2-like macrophages; TAMs; TME; Pediatric solid tumor

摘要：Neuroblastoma (NB) is the most common and deadliest extracranial solid tumor in children. Targeting tumor-associated macrophages (TAMs) is a strategy for attenuating tumor-promoting states. The crosstalk between cancer cells and TAMs plays a pivotal role in mediating tumor progression in NB. The overexpression of Hexokinase-3 (HK3), a pivotal enzyme in glucose metabolism, has been associated with poor prognosis in NB patients. Furthermore, it correlates with the infiltration of M2-like macrophages within NB tumors, indicating its significant involvement in tumor progression. Therefore, HK3 not only directly regulates the malignant biological behaviors of tumor cells, such as proliferation, migration, and invasion, but also recruits and polarizes M2-like macrophages through the PI3K/AKT-CXCL14 axis in neuroblastoma. The secretion of lactate and histone lactylation alterations within tumor cells accompanies this interaction. Additionally, elevated expression of HK3 in M2-TAMs was found at the same time. Modulating HK3 within M2-TAMs alters the biological behavior of tumor cells, as demonstrated by our in vitro studies. This study highlights the pivotal role of HK3 in the progression of NB malignancy and its intricate regulatory network with M2-TAMs. It establishes HK3 as a promising dual-functional biomarker and therapeutic target in combating neuroblastoma.

基金机构：Science and Technology Innovation Key R&D Program of Chongqing

基金资助正文：Not applicable.