LHPP对乳腺癌细胞功能的影响以及在免疫调控中的作用*

doi:10.3870/j.issn.1672-0741.25.09.045

华中科技大学学报（医学版） ›› 2026, Vol. 55 ›› Issue (1): 97-103.doi: 10.3870/j.issn.1672-0741.25.09.045

LHPP对乳腺癌细胞功能的影响以及在免疫调控中的作用^*

向敏¹, 葛彦锋², 蒋一凡¹, 邹一辰¹, 张龙锋¹, 庄秀芬³, 舒扬^1△

江苏大学附属医院 ¹检验科 ²血管外科 ³肿瘤科, 镇江 212001

收稿日期:2025-09-23 出版日期:2026-02-15 发布日期:2026-02-10
通讯作者: ^△E-mail:ushyang@ujs.edu.cn
作者简介:向敏,女,1985年生,医学硕士,主管技师,E-mail:zlxiang43@163.com
基金资助:
^*国家自然科学基金资助项目(No.81402442);镇江市社会发展指导性科技计划项目(No.FZ2023055,No.FZ2024061);镇江市重点研发计划资助项目(No.SH2023003)

The Role of LHPP in Breast Cancer Cell Function and Immune Regulation

Xiang Min¹, Ge Yanfeng², Jiang Yifan¹ et al

¹Department of Clinical Laboratory, ²Department of Vascular Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, China

Received:2025-09-23 Online:2026-02-15 Published:2026-02-10
Contact: ^△E-mail:ushyang@ujs.edu.cn

摘要/Abstract

摘要： 目的检测磷酸赖氨酸磷酸组氨酸无机焦磷酸性磷酸酶(LHPP)在人乳腺癌中的表达水平,分析其对乳腺癌细胞增殖与迁移的影响,并初步探讨其在免疫调控中的潜在作用。方法采用免疫组织化学法检测乳腺癌患者癌组织及配对癌旁组织中LHPP蛋白的表达水平。选取不同LHPP表达水平的乳腺癌细胞系(T47D,MCF7),分别构建LHPP过表达(T47D)及敲低(MCF7)细胞模型。通过Western blot和qPCR检测LHPP蛋白及mRNA表达水平;利用CCK-8和Transwell实验评估细胞增殖及迁移能力;同时检测p-Akt/Akt通路关键蛋白的变化。通过生物信息学分析LHPP对肿瘤微环境相关免疫细胞的影响。结果 LHPP在乳腺癌组织中的表达水平显著低于配对癌旁组织(P<0.05)。在细胞系中,T47D细胞的LHPP表达水平较低,而MCF7细胞则较高(均P<0.05)。功能实验表明:在T47D细胞中过表达LHPP后,细胞增殖、迁移能力及p-Akt/Akt相对量均显著降低(均P<0.05);反之,在MCF7细胞中敲低LHPP后,上述细胞表型及Akt通路活性均显著增强(均P<0.05),生物信息学分析提示LHPP可能通过调控免疫细胞影响肿瘤进展。结论 LHPP在乳腺癌中表达下调,可能作为一种抑癌基因,通过抑制Akt信号通路活性进而阻碍乳腺癌细胞的增殖与迁移能力,并可能在肿瘤免疫调控中发挥作用。

关键词: LHPP, 乳腺癌, 细胞增殖, 细胞迁移, Akt, 肿瘤微环境

Abstract: Objective To investigate the expression level of LHPP in human breast cancer and its impact on proliferation and migration and to conduct a preliminary exploration of its immunoregulatory function. Methods The expression level of the LHPP protein was examined in breast cancer patients.To manipulate LHPP expression,breast cancer cells were transfected with overexpression plasmids (T47D) or specific shRNAs(MCF7).LHPP protein levels,along with cell proliferation,migration capacity,and Akt pathway activity,were quantified via Western blotting,CCK-8,Transwell,and related assays,respectively.A preliminary investigation was conducted to examine the role of LHPP in immune regulation. Results The expression was significantly lower in cancer tissues than in adjacent non-tumor tissues from breast cancer patients(P<0.05).LHPP expression varied across cancer cell lines,with T47D showing lower levels and MCF7 exhibiting relatively higher levels(all P<0.05).In T47D cells,LHPP overexpression successfully led to increased levels of LHPP.As a result,cell proliferation,migration,and the p-Akt/Akt ratio were significantly decreased(all P<0.05).In MCF7 cells,shLHPP transfection knocked down LHPP expression,leading to significant changes in the above-mentioned phenotypic and pathway markers(all P<0.05). Conclusion LHPP,which is expressed at low levels in breast cancer,functions as a tumor suppressor by inhibiting cancer cell proliferation and migration.This effect may be mediated through the Akt signaling pathway.

Key words: LHPP, breast cancer, cell proliferation, cell migration, Akt, microenvironment

中图分类号:

R737.9

向敏, 葛彦锋, 蒋一凡, 邹一辰, 张龙锋, 庄秀芬, 舒扬. LHPP对乳腺癌细胞功能的影响以及在免疫调控中的作用^*[J]. 华中科技大学学报（医学版）, 2026, 55(1): 97-103.

Xiang Min, Ge Yanfeng, Jiang Yifan et al. The Role of LHPP in Breast Cancer Cell Function and Immune Regulation[J]. Acta Medicinae Universitatis Scientiae et Technologiae Huazhong, 2026, 55(1): 97-103.

参考文献

[1] Hindupur S K,Colombi M,Fuhs S R,et al.The protein histidine phosphatase LHPP is a tumour suppressor[J].Nature,2018,555(7698):678-682.
[2] Xie G,Li N,Li K,et al.Phosphatase LHPP confers prostate cancer ferroptosis activation by modulating the AKT-SKP2-ACSL4 pathway[J].Cell Death Dis,2024,15(9):665.
[3] Guo L,Chen W,Yue J,et al.Unlocking the potential of LHPP:Inhibiting glioma growth and cell cycle via the MDM2/p53 pathway[J].Biochim Biophys Acta Mol Basis Dis,2025,1871(1):167509.
[4] Wang D,Li J,Li W.LHPP suppresses gastric cancer progression via the PI3K/AKT/mTOR signaling pathway[J].J Cancer,2022,13(14):3584-3592.
[5] Bindea G,Mlecnik B,Tosolini M,et al.Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer[J].Immunity,2013,39(4):782-795.
[6] Xiong X,Zheng LW,Ding Y,et al.Breast cancer:pathogenesis and treatments[J].Signal Transduct Target Ther,2025,10(1):49.
[7] Wu J,Fan D,Shao Z,et al.CACA guidelines for holistic integrative management of breast Cancer[J].Holist Integr Oncol,2022,1(7):7.
[8] Visvader J E,Lindeman G J.Cancer stem cells in solid tum-ours:accumulating evidence and unresolved questions[J].Nat Rev Cancer,2008,8(10):755-768.
[9] Stevens R G,Brainard G C,Blask D E,et al.Breast cancer and circadian disruption from electric lighting in the modern world[J].CA Cancer J Clin,2014,64(3):207-218.
[10] Nejman D,Livyatan I,Fuks G,et al.The human tumor microbiome is composed of tumor type-specific intracellular bacteria[J].Science,2020,368(6494):973-980.
[11] Fuhs S R,Hunter T.Phosphorylation:The emergence of histidine phosphorylation as a reversible regulatory modification[J].Curr Opin Cell Biol,2017,45:8-16.
[12] Ma L,Sun H,Xu X,et al.Tumor suppressor LHPP suppresses cell proliferation and epithelial-mesenchymal transition in hepatocellular carcinoma cell lines[J].J Physiol Biochem,2022,78(4):807-817.
[13] Gao K,Yin N,Shen Z,et al.LHPP promotes the intracellular reactive oxygen species accumulation and sensitivity of gastric cancer to cisplatin via JNK and p38 MAPK pathways[J].Histol Histopathol,2023,38(9):1055-1068.
[14] Hou B,Li W,Xia P,et al.LHPP suppresses colorectal cancer cell migration and invasion in vitro and in vivo by inhibiting Smad3 phosphorylation in the TGF-β pathway[J].Cell Death Discov,2021,7(1):273.
[15] Zhao Y,Liu H,Zhan Q,et al.Oncolytic adenovirus encoding LHPP exerts potent antitumor effect in lung cancer[J].Sci Rep,2024,14(1):13108.
[16] Li J,Xie H,Ying Y,et al.YTHDF2 mediates the mRNA degradation of the tumor suppressors to induce AKT phosphorylation in N6-methyladenosine-dependent way in prostate cancer[J].Mol Cancer,2020,19(1):152.
[17] Wang X,Cheng H,Zhao J,et al.Long noncoding RNA DLGAP1-AS2 promotes tumorigenesis and metastasis by regulating the Trim21/ELOA/LHPP axis in colorectal cancer[J].Mol Cancer,2022,21(1):210.
[18] Shen M,Cao S,Long X,et al.DNAJC12 causes breast cancer chemotherapy resistance by repressing doxorubicin-induced ferroptosis and apoptosis via activation of AKT[J].Redox Biol,2024,70:103035.
[19] Luboff A J,DeRemer D L.Capivasertib:A novel AKT inhibitor approved for hormone-receptor-positive,HER-2-negative metastatic breast cancer[J].Ann Pharmacother,2024,58(12):1229-1237.
[20] Barriga V,Kuol N,Nurgali K,et al.The complex interaction between the tumor micro-environment and immune checkpoints in breast cancer[J].Cancers(Basel),2019,11(8):1205.

LHPP对乳腺癌细胞功能的影响以及在免疫调控中的作用^*

The Role of LHPP in Breast Cancer Cell Function and Immune Regulation

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	黄丽云, 覃柳宇, 蒋运, 牛晓辉, 杨健叶, 龚静. 乳腺癌可选择性多聚腺苷酸化及其相关因素系统分析^*[J]. 华中科技大学学报（医学版）, 2026, 55(1): 34-44.
[2]	吕九娣, 彭昕, 邢玉广, 王俊杰, 胡军红. 紫花前胡素通过miR-17-5p靶向PI3K/Akt通路对结直肠癌细胞增殖和迁移的影响^*[J]. 华中科技大学学报（医学版）, 2026, 55(1): 76-81.
[3]	孙阳, 范小勇, 陈红伟. miR-199a-5p靶向 Akt/eNOS信号通路促进应激性心肌病大鼠心脏功能障碍[J]. 华中科技大学学报（医学版）, 2025, 54(6): 828-834.
[4]	许腊梅, 凌锐, 汤翔, 陈伟豪, 孙康△ , 徐岷. 半胱氨酸蛋白酶抑制剂2在结直肠癌中的表达及其与患者预后的相关性分析[J]. 华中科技大学学报（医学版）, 2025, 54(6): 835-841.
[5]	郭若楠, 向敏, 武晓白, 王韵, 蒋一凡, 周月鹏, 舒扬. KCNJ14在神经胶质瘤细胞中的表达及其对细胞增殖的影响[J]. 华中科技大学学报（医学版）, 2025, 54(5): 665-671.
[6]	杨磊, 王剑明. 胆管癌中的非遗传异质性与耐药[J]. 华中科技大学学报（医学版）, 2025, 54(5): 738-742.
[7]	谭凤娇, 霍博, 蒋丁胜, 方泽民. HDAC3-Akt通路在血管平滑肌细胞增殖中的作用[J]. 华中科技大学学报（医学版）, 2025, 54(4): 465-469.
[8]	韩晓晴, 沈达, 孙纪威, 曹亚茹, 杜露阳, 朱磊, 郭丰源. 三级淋巴结构在口腔鳞状细胞癌中的研究进展: 从基础特征到临床意义[J]. 华中科技大学学报（医学版）, 2025, 54(4): 579-586.
[9]	代新珍, 汤红平, 袁理, 米贤军, 钟守军, 陈志强, 邓文同. CD99在乳腺癌组织中的表达及对乳腺癌细胞增殖和迁移的影响[J]. 华中科技大学学报（医学版）, 2025, 54(3): 352-356.
[10]	赵培, 杜小祥, 庄晓飞, 郭石平. 中性粒细胞外诱捕网与食管癌关系的研究进展[J]. 华中科技大学学报（医学版）, 2025, 54(3): 447-451.
[11]	李潇, 赵博, 郭研, 徐壮语, 徐繁. C1q样蛋白4对乳腺癌侵袭及转移影响的体内研究[J]. 华中科技大学学报（医学版）, 2025, 54(2): 203-210.
[12]	孙小虎, 王柯乜, 曹旭晨. 中药姜黄素代谢产物四氢姜黄素抗乳腺癌Hormesis效应的剂量学分析[J]. 华中科技大学学报（医学版）, 2025, 54(1): 8-12.
[13]	王韵, 舒扬, 武晓白, 郭若楠, 黄汉鹏, 向敏. NPM3在肺腺癌中的表达及其对肺腺癌细胞生物学功能的影响[J]. 华中科技大学学报（医学版）, 2025, 54(1): 36-44.
[14]	赵海南, 周丽娜. MVP对人肾癌细胞功能的影响及机制研究[J]. 华中科技大学学报（医学版）, 2024, 53(5): 629-634.
[15]	周方, 卢喜科, 李月川. OMA1基因对人肺腺癌细胞增殖、迁移、侵袭和凋亡的作用及机制研究[J]. 华中科技大学学报（医学版）, 2024, 53(4): 458-465.