Diagnostic and Therapeutic Center for Breast Disease, The Fourth Hospital of Hebei Medical University.
The Second Department of Thyroid and Breast Surgery, Cangzhou Central Hospital.
Biol Pharm Bull. 2023;46(2):209-218. doi: 10.1248/bpb.b22-00595.
Triple-negative breast cancer (TNBC) puts a great threat to women's health. GLIS family zinc finger 3 (GLIS3) belongs to the GLI transcription factor family and acts as a critical factor in cancer progression. Nevertheless, the part of GLIS3 played in TNBC is not known. Immunohistochemical (IHC) staining analysis displayed that GLIS3 was highly expressed in TNBC tissues. The effect of GLIS3 on the malignant phenotype of TNBC was tested in two different cell lines according to GLIS3 regulation. Upregulation of GLIS3 promoted the proliferation, migration, and invasion of TNBC cell lines, whereas the knockdown of GLIS3 suppressed these tumor activities. Inhibition of GLIS3 induced TNBC cell apoptosis. Furthermore, study as immunofluorescence and electrophoretic mobility shift assay confirmed that the nuclear factor-κB (NF-κB) signaling pathway activated by GLIS3 played an important role in TNBC cells' malignant phenotype. In conclusion, the present work demonstrated that GLIS3 acts as a crucial element in TNBC progression via activating the NF-κB signaling pathway. Accordingly, above mentioned findings indicated that modulation of GLIS3 expression is a potential tactic to interfere with the progression of TNBC.
三阴性乳腺癌(TNBC)对女性健康构成了巨大威胁。GLIS 家族锌指蛋白 3(GLIS3)属于 GLI 转录因子家族,是癌症进展的关键因素。然而,GLIS3 在 TNBC 中的作用尚不清楚。免疫组织化学(IHC)染色分析显示,GLIS3 在 TNBC 组织中高度表达。根据 GLIS3 调控,在两种不同的细胞系中测试了 GLIS3 对 TNBC 恶性表型的影响。上调 GLIS3 促进了 TNBC 细胞系的增殖、迁移和侵袭,而 GLIS3 的敲低则抑制了这些肿瘤活性。抑制 GLIS3 诱导 TNBC 细胞凋亡。此外,研究免疫荧光和电泳迁移率变动分析证实,GLIS3 激活的核因子-κB(NF-κB)信号通路在 TNBC 细胞的恶性表型中发挥重要作用。总之,本研究表明,GLIS3 通过激活 NF-κB 信号通路在 TNBC 进展中发挥关键作用。因此,上述发现表明调节 GLIS3 的表达可能是一种潜在的策略,可以干扰 TNBC 的进展。