GALNT14 通过与 GDF-15 结合促进乳腺癌干细胞特性和耐药性形成，并通过β-catenin 信号通路发挥作用。

GALNT14 in association with GDF-15 promotes stemness and drug resistance through β-catenin signalling pathway in breast cancer.

机构信息

Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, 342005, India.

Department of Oncosurgery, All India Institute of Medical Sciences, Jodhpur, India.

出版信息

Mol Biol Rep. 2024 May 25;51(1):691. doi: 10.1007/s11033-024-09645-9.

DOI:10.1007/s11033-024-09645-9

PMID:38796671

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

背景

糖基化修饰的改变在癌症发生中起作用。GALNT14 促进癌症干细胞样特性和耐药性。已知 GDF-15 诱导乳腺癌（BC）干细胞样细胞状态的耐药性和干性标志物。目前缺乏 GDF-15 和 GALNTs 之间关联的数据。在这项研究中，评估了 BC 中 GALNT14 和 GDF-15 与干性（OCT4 和 SOX2）和耐药性（ABCC5）标志物的表达和相互作用。

方法

我们研究了 30 名 BC 患者和相邻非肿瘤组织的肿瘤组织。评估了 BC 患者和匹配的健康对照者血清中的 GALNT14 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 测定 β-catenin 的基因表达和蛋白表达。

结果

与相邻非肿瘤组织相比，BC 肿瘤组织中 GALNT14、GDF-15、OCT4、SOX2、ABCC5 和 β-catenin 的表达显著增加。BC 患者的血清 GALNT14 水平明显高于健康对照组（80.7±65.3pg/ml 比 12.2±9.12pg/ml）（p<0.000）。为了进一步分析参与 BC 干性和耐药性的信号通路，在 MCF-7 细胞系中敲低 GALNT14 和 GDF-15，观察到敲低后 OCT4、SOX2、ABCC5 和 β-catenin 的表达水平降低，并且与 GALNT14 和 GDF-15 的共敲低进一步降低了基因的表达。