集成技术2026，Vol.15Issue(1)：41-55,15.DOI:10.12146/j.issn.2095-3135.20250828001
DLG3通过调控STAT3活化促进乳腺癌细胞的增殖和迁移
DLG3 Promotes Breast Cancer Cell Proliferation and Migration by Mediating STAT3 Activation
摘要
Abstract
Breast cancer(BRCA)is characterized by high heterogeneity,with aggressive subtypes frequently showing poor prognosis and resistance to conventional therapies,making the discovery of new therapeutic targets and strategies imperative.Although elevated expression of discs large homolog 3(DLG3)has been reported in BRCA,its functional role in disease progression remains unclear.We performed bioinformatic analyses of clinical datasets to evaluate the prognostic significance of DLG3 expression in BRCA patients.In vitro gain-and loss-of-function experiments were conducted to assess the impact of DLG3 on BRCA cell proliferation,migration,and colony formation.Transcriptomic profiling,coupled with pharmacological inhibition,was employed to identify and validate downstream signaling pathways.Additionally,we extended our validation to an in vivo model to assess the role of DLG3 in tumor progression.We found that elevated DLG3 levels correlated with poor prognosis in breast cancer patients.Functionally,DLG3 overexpression significantly promoted cell proliferation and migration in estrogen receptor-positive MCF7 and triple-negative MDA-MB-231 breast cancer cells,whereas its knockdown suppressed these effects.Transcriptomic analyses revealed that DLG3 activates signal transducer and activator of transcription 3(STAT3)signaling,a finding further corroborated by Western blot.Critically,treatment with the STAT3 inhibitor Stattic attenuated DLG3-driven proliferation and migration,supporting a DLG3-STAT3 oncogenic axis.Furthermore,in vivo studies validated the role of DLG3 in promoting tumor growth and its correlation with elevated STAT3 signaling,consistent with our in vitro findings.Our findings establish DLG3 as a novel driver of breast cancer progression that directly activates STAT3 signaling.DLG3 thus represents both a potential prognostic biomarker and a promising therapeutic target for aggressive breast cancer subtypes,including triple-negative breast cancer.关键词
乳腺癌/DLG3/信号转导及转录激活因子3/增殖/迁移Key words
breast cancer/DLG3/STAT3/proliferation/migration分类
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Khalid Idris GIDADO,Rabiu LAWAN,彭喜霞,张子洋,万晓春,卢珍,章桂忠..DLG3通过调控STAT3活化促进乳腺癌细胞的增殖和迁移[J].集成技术,2026,15(1):41-55,15.基金项目
广东省基础与应用基础研究基金项目(2021A1515110053,2023A1515030028) （2021A1515110053,2023A1515030028）
深圳市科技计划项目(JCYJ20210324101402007,JCYJ20220818100806015) This work is supported by Guangdong Basic and Applied Basic Research Foundation(2021A1515110053,2023A1515030028)and Shenzhen Science and Technology Program(JCYJ20210324101402007,JCYJ20220818100806015) （JCYJ20210324101402007,JCYJ20220818100806015）
