文章：

Cx43介导的自噬机制通过调控Rab31影响三阴性乳腺癌

The Cx43-Mediated Autophagy Mechanism Influences Triple-Negative Breast Cancer Through the Regulation of Rab31

原文发布日期：8 December 2025

DOI: 10.3390/cancers17243923

类型: Article

开放获取: 是

英文摘要：

Background:Connexin43 (Cx43) is recognized as a transmembrane protein; its precise expression profile and molecular mechanisms in triple-negative breast cancer (TNBC) remain unclear.Methods:We systematically analyzed Cx43 expression in over 60 breast cancer cell lines from the CCLE and HPA databases. Immunohistochemical evaluation compared Cx43 expression between TNBC tissues and adjacent normal tissues. Cx43 expression was assessed in normal breast epithelial cells (MCF-10A) and two TNBC cell lines (MDA-MB-231 and BT-549) using qRT-PCR and Western blot. Functional assays (CCK8, wound healing, transwell) evaluated TNBC progression following Cx43 interference or overexpression. Rab31, a Cx43-interacting protein, was identified via bioinformatics, immunofluorescence, and Co-IP. Autophagy-related proteins (ULK1, ATG5, LC3, and p62) were analyzed after Cx43 or Rab31 modulation. Finally, a nude mouse model validated Cx43’s in vivo effects on tumor growth and associated molecular changes.Results:Cx43 was upregulated in TNBC tissues and cell lines. Overexpression enhanced proliferation, migration, and invasion, while knockdown suppressed these effects. Cx43 co-expressed with Rab31, regulating its protein levels and autophagy. Rab31 interference reversed Cx43-mediated autophagy and oncogenic behaviors. In vivo, Cx43 promoted tumor growth and modulated Rab31/autophagy pathways.Conclusions:The Cx43/Rab31 axis drives autophagy to facilitate TNBC progression, highlighting Cx43 as a potential therapeutic target. Our findings provide mechanistic insights for improving TNBC treatment.

摘要翻译： 

背景：连接蛋白43（Cx43）被确认为一种跨膜蛋白，但其在三阴性乳腺癌（TNBC）中的精确表达谱及分子机制尚不明确。方法：我们系统分析了CCLE和HPA数据库中60余种乳腺癌细胞系的Cx43表达情况。通过免疫组化评估比较了TNBC组织与癌旁正常组织中Cx43的表达差异。采用qRT-PCR和Western blot检测了正常乳腺上皮细胞（MCF-10A）及两种TNBC细胞系（MDA-MB-231和BT-549）中Cx43的表达水平。通过功能实验（CCK8、划痕愈合、Transwell）评估了干扰或过表达Cx43对TNBC进展的影响。利用生物信息学分析、免疫荧光及免疫共沉淀技术鉴定了与Cx43相互作用的蛋白Rab31。在调控Cx43或Rab31后，检测了自噬相关蛋白（ULK1、ATG5、LC3和p62）的表达变化。最后，通过裸鼠模型验证了Cx43在体内对肿瘤生长及相关分子通路的影响。结果：Cx43在TNBC组织及细胞系中表达上调。过表达Cx43可增强细胞增殖、迁移和侵袭能力，而敲低Cx43则抑制这些恶性表型。Cx43与Rab31存在共表达，并能调控Rab31蛋白水平及自噬过程。干扰Rab31可逆转Cx43介导的自噬及促癌效应。体内实验表明，Cx43能促进肿瘤生长并调控Rab31/自噬通路。结论：Cx43/Rab31轴通过驱动自噬促进TNBC进展，提示Cx43可作为潜在治疗靶点。本研究为改善TNBC治疗策略提供了机制依据。

原文链接：

The Cx43-Mediated Autophagy Mechanism Influences Triple-Negative Breast Cancer Through the Regulation of Rab31