Wang Lu, Zhang Lifen, Luo Pei, Xia Zeyu, Shao Shan, Ning Qian, Gu Shanzhi, Zhao Xinhan, Luo Minna
Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, 710061, China.
School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, Shaanxi Province, 710061, China.
Curr Cancer Drug Targets. 2025;25(5):509-519. doi: 10.2174/0115680096303983240616191051.
Triple-Negative Breast Cancer (TNBC) accounts for 15-20% of all breast cancers and approximately 50% of breast cancer deaths. Chemotherapy remains the mainstay of systemic treatment due to the lack of effective therapy targets. Thus, more studies are urgently needed to identify new therapeutic targets in TNBC patients.
GAPVD1 expression and prognosis value in breast cancer samples were explored in The Cancer Genome Atlas database (TCGA). GAPVD1 knockdown and overexpression TNBC cell lines were constructed. CCK-8 and colony formation assays were performed to detect cell viability. Flow cytometry analysis was performed to detect cell cycle variation. Western blotting was conducted to determine the levels of target genes. Finally, an enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed.
GAPVD1 is overexpressed in breast cancer tissues and predicts poor prognosis. experiments demonstrated that GAPVD1 is correlated with cell proliferation and the cell cycle of TNBC cells. Mechanistically, alteration in GAPVD1 expression was found to be associated with cell cycle-related proteins PCNA, Cyclin A, and the activity of the ERK/MAPK signaling pathway. Consistent with these findings, enrichment analysis of GAPVD1-involving partners and signaling pathways revealed that the cellular biosynthetic process, macromolecule biosynthetic process, and cell cycle signaling are related to GAPVD1. experiment demonstrated that GAPVD1 inhibition impedes tumor growth and expression of cell cycle-related proteins.
Taken together, our results indicate that GAPVD1 may participate in TNBC cell growth by regulating the cell cycle and ERK/MAPK signaling pathway.
三阴性乳腺癌（TNBC）占所有乳腺癌的15%-20%，约占乳腺癌死亡病例的50%。由于缺乏有效的治疗靶点，化疗仍然是全身治疗的主要手段。因此，迫切需要更多研究来确定TNBC患者的新治疗靶点。
在癌症基因组图谱数据库（TCGA）中探索GAPVD1在乳腺癌样本中的表达及预后价值。构建GAPVD1敲低和过表达的TNBC细胞系。进行CCK-8和集落形成试验以检测细胞活力。进行流式细胞术分析以检测细胞周期变化。进行蛋白质免疫印迹法以确定靶基因的水平。最后，进行基因本体论（GO）富集分析和京都基因与基因组百科全书（KEGG）分析。
GAPVD1在乳腺癌组织中过表达，并预示预后不良。实验表明，GAPVD1与TNBC细胞的增殖和细胞周期相关。机制上，发现GAPVD1表达的改变与细胞周期相关蛋白PCNA、细胞周期蛋白A以及ERK/MAPK信号通路的活性有关。与这些发现一致，对涉及GAPVD1的伙伴和信号通路的富集分析表明，细胞生物合成过程、大分子生物合成过程和细胞周期信号传导与GAPVD1相关。实验表明，抑制GAPVD1可阻碍肿瘤生长和细胞周期相关蛋白的表达。
综上所述，我们的结果表明，GAPVD1可能通过调节细胞周期和ERK/MAPK信号通路参与TNBC细胞的生长。
