Page 30 - 南京医科大学自然版

南京医科大学学报（自然科学版） 第46卷第5期
·652 · Journal of Nanjing Medical University（Natural Sciences） 2026年5月

·基础研究·

PTPN6在胃癌中的作用及对NK细胞介导杀伤活性的影响

王心雅 ，罗 琳 ，高 乾 ，颜财旺 1，2*
2
2
1
南京医科大学基础医学院免疫学系，公共卫生学院流行病学系，江苏 南京 211166
1 2

［摘 要］ 目的：探究蛋白酪氨酸磷酸酶非受体型6（tyrosine protein phosphatase non⁃receptor type 6，PTPN6）在胃癌组织中的
表达特征，评估其与自然杀伤（natural killer，NK）细胞浸润与活化的相关性，并进一步阐明PTPN6对胃癌细胞增殖等恶性表型
及NK细胞杀伤活性的调控作用和分子机制。方法：基于亚洲癌症研究组（Asian Cancer Research Group，ACRG）及整合单细胞数
据，分析PTPN6在胃癌组织中的表达水平，及其与NK细胞浸润和活化水平的相关性；采用CCK⁃8、EdU、克隆形成及Transwell实
验评估沉默或过表达PTPN6对MKN1和AGS细胞增殖、迁移和侵袭的影响；通过流式细胞术检测各组细胞凋亡水平和NK细
胞介导的杀伤效率；通过qRT⁃PCR 检测各组细胞人类白细胞抗原⁃Ⅰ类（human leukocyte antigen ⁃ class Ⅰ，HLA⁃Ⅰ）分子的表
达水平；通过全外显子测序评估胃癌类器官与原发组织在基因组层面的相似性，通过胃癌类器官和NK细胞共培养模型评估
NK细胞杀伤效率；构建PTPN6过表达的YTN16胃癌细胞系，在NCG鼠和C57BL/6鼠中进行皮下荷瘤，通过流式细胞术对肿瘤
浸润NK细胞进行分析；通过转录组测序鉴定PTPN6调控的潜在下游分子和信号通路。结果：PTPN6在胃癌组织中表达显著
上调，且与NK细胞的浸润和活化水平呈显著负相关；敲低PTPN6可抑制胃癌细胞增殖能力，增强NK细胞杀伤敏感性，并下调
HLA⁃Ⅰ类分子表达；过表达PTPN6则促进胃癌细胞恶性表型，减弱NK细胞杀伤活性，同时上调HLA⁃Ⅰ类分子表达；小鼠荷瘤
体内实验显示，过表达 PTPN6 可加速 C57BL/6 小鼠肿瘤生长，并使肿瘤组织的 NK 细胞浸润比例减少；转录组测序分析表明
PTPN6过表达激活PI3K/AKT、MYC 和NF⁃κB等信号通路。结论：PTPN6在胃癌中高表达，通过激活PI3K/AKT 等信号通路促
进肿瘤细胞增殖和侵袭；其表达与NK细胞浸润和活化水平呈负相关，可通过调控胃癌细胞HLA⁃Ⅰ类分子表达介导免疫逃逸。
［关键词］ 胃癌；NK细胞；PTPN6
［中图分类号］ R735.2 ［文献标志码］ A ［文章编号］ 1007⁃4368（2026）05⁃652⁃13
doi：10.7655/NYDXBNSN251034

The role of PTPN6 in gastric cancer and its impact on NK cell⁃mediated cytotoxicity

1 2 2 1，2*
WANG Xinya ，LUO Lin ，GAO Qian ，YAN Caiwang
Department of Immunology，School of Basic Medicine，Department of Epidemiology，School of Public Health，
1 2
Nanjing Medical University，Nanjing 211166，China

［Abstract］ Objective：To investigate the expression characteristics of protein tyrosine phosphatase non⁃receptor type 6（PTPN6）in
gastric cancer tissues，evaluate its correlation with natural killer（NK）cell infiltration and activation，and further elucidate the
regulatory role and molecular mechanisms of PTPN6 in malignant phenotypes such as gastric cancer cell proliferation and that in NK
cell cytotoxic activity. Methods：Based on the Asian Cancer Research Group（ACRG）gastric cancer cohort and integrated single⁃cell
data，the expression level of PTPN6 in gastric cancer tissues and its correlation with NK cell infiltration and activation levels were
analyzed. CCK⁃8，EdU，colony formation，and Transwell assays were used to evaluate the effects of silencing or overexpressing PTPN6
on the proliferation，migration，and invasion of MKN1 and AGS cells. Flow cytometry was employed to detect apoptosis levels and NK
cell⁃mediated killing efficiency. qRT⁃PCR was used to measure the expression levels of human leukocyte antigen⁃class I（HLA⁃I）
molecules. Whole ⁃ exome sequencing was applied to assess the genomic similarity between gastric cancer organoids and primary
tissues，and a co⁃culture model of gastric cancer organoids and NK cells was used to evaluate NK cell killing efficiency. A PTPN6⁃
overexpressing YTN16 gastric cancer cell line was constructed and subcutaneously inoculated into NCG and C57BL/6 mice，followed
by flow cytometric analysis of tumor⁃infiltrating NK cells. Transcriptome sequencing was performed to identify potential downstream

［基金项目］ 国家自然科学基金（82574185）
通信作者（Corresponding author），E⁃mail：caiwangyan@njmu.edu.cn.（ORCID：0000⁃0002⁃3488⁃4305）
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