GALNT14 与 GDF-15 联合通过 β-catenin 信号通路促进乳腺癌的干细胞性和耐药性。
GALNT14 in association with GDF-15 promotes stemness and drug resistance through β-catenin signalling pathway in breast cancer.
发表日期:2024 May 25
作者:
Ashita Gadwal, Purvi Purohit, Manoj Khokhar, Jeewan Ram Vishnoi, Puneet Pareek, Ramkaran Choudhary, Poonam Elhence, Mithu Banerjee, Praveen Sharma
来源:
CYTOKINE & GROWTH FACTOR REVIEWS
摘要:
糖基化改变在致癌过程中发挥作用。 GALNT14 促进癌症干细胞样特性和耐药性。 GDF-15 已知可诱导耐药性和干细胞标记物,以维持乳腺癌 (BC) 干细胞样细胞状态。目前缺乏 GDF-15 与 GALNT 关联的数据。在本研究中,评估了 BC 中 GALNT14 和 GDF-15 的表达及其与干性(OCT4 和 SOX2)和耐药性(ABCC5)标记物的相互作用。我们研究了 30 名 BC 患者的肿瘤组织和邻近的非肿瘤组织。评估了 BC 患者和匹配的健康对照者血清 GALNT14 的表达。通过 RT-PCR 测定 BC 组织中 GALNT14、GDF-15、OCT4、SOX2、ABCC5 和 β-catenin 的表达。通过siRNA敲低MCF-7细胞系中的GALNT14和GDF-15,通过western blot检测β-catenin的基因表达和蛋白表达。GALNT14、GDF-15、OCT4、SOX2的表达显着增加与邻近的非肿瘤组织相比,在 BC 肿瘤组织中观察到了 、ABCC5 和 β-连环蛋白。与健康对照者 (12.2±9.12 pg/ml) 相比,BC 患者的 GALNT14 血清水平显着升高 (80.7±65.3 pg/ml) (p<0.000)。为了进一步分析BC干性和耐药性中涉及的信号通路,在MCF-7细胞系中敲低GALNT14和GDF-15,观察敲低后OCT4、SOX2、ABCC5和β的表达水平-catenin 降低,与 GALNT14 和 GDF-15 共同敲低进一步降低基因表达。可以得出结论,GALNT14 与 GDF-15 联合,可能通过 β- 促进 BC 的干性和内在耐药性。连环蛋白信号通路。© 2024。作者获得 Springer Nature B.V. 的独家许可。
Altered glycosylation plays a role in carcinogenesis. GALNT14 promotes cancer stem-like properties and drug resistance. GDF-15 is known to induces drug resistance and stemness markers for maintenance of breast cancer (BC) stem-like cell state. Currently there is lack of data on association of GDF-15 and GALNTs. In this study, the expression and interaction of GALNT14 and GDF-15 with stemness (OCT4 and SOX2) and drug resistance (ABCC5) markers were evaluated in BC.We investigated tumour tissue from 30 BC patients and adjacent non-tumour tissues. Expression of serum GALNT14 from BC patients and matched healthy controls was evaluated. Expression of GALNT14, GDF-15, OCT4, SOX2, ABCC5, and β-catenin in BC tissue was determined by RT-PCR. Knockdown of GALNT14 and GDF-15 in the MCF-7 cell line was done through siRNA, gene expression and protein expression of β-catenin by western blot were determined.A significant increase in the expression of GALNT14, GDF-15, OCT4, SOX2, ABCC5, and β-catenin was observed in BC tumour tissues compared to adjacent non-tumour tissues. The serum level of GALNT14 was significantly high in BC patients (80.7 ± 65.3 pg/ml) compared to healthy controls (12.2 ± 9.12 pg/ml) (p < 0.000). To further analyse the signalling pathway involved in BC stemness and drug resistance, GALNT14 and GDF-15 were knocked down in the MCF-7 cell line, and it was observed that after knockdown, the expression level of OCT4, SOX2, ABCC5, and β-catenin was decreased, and co-knockdown with GALNT14 and GDF-15 further decreased the expression of genes.It can be concluded that GALNT14, in association with GDF-15, promotes stemness and intrinsic drug resistance in BC, possibly through the β-catenin signalling pathway.© 2024. The Author(s), under exclusive licence to Springer Nature B.V.