由ST6GAL1诱导EGFR的化诱导受体激活,并调节贩运动态
Katherine E Ankenbauer1, Tejeshwar C Rao1, Alexa L Mattheyses1
1Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL.
bioRxiv : the preprint server for biology
|July 3, 2023
概括
异常的糖化,特别是由ST6GAL1指导的α2,6化增加,通过激活表皮生长因子受体 (EGFR) 信号通过增强的二分化和回收来促进卵巢癌.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
背景情况:
- 异常的糖化是癌症的标志性特征,α2,6糖化通常是丰富的.
- 在许多癌症中,包括卵巢癌中,ST6GAL1酸转移酶可调节α2,6酸转移.
- 已知表皮生长因子受体 (EGFR) 的α2,6化会激活它,但机制尚不清楚.
研究的目的:
- 研究ST6GAL1在调节卵巢癌EGFR激活和信号传导中的作用.
- 阐明ST6GAL1影响EGFR活性,二元化和贩运的分子机制.
主要方法:
- 在卵巢癌细胞系 (OV4,OVCAR-3,OVCAR-5) 中,ST6GAL1的过度表达和抑制.
- 评估EGFR激活和下游信号 (AKT,NFκB).
- 使用生物化学分析,全内反射光显微镜 (TIRF) 和3D宽场解卷显微镜来分析EGFR二分化,寡聚化和贩运动态 (与Rab11和LAMP1共同定位).
主要成果:
- 高ST6GAL1表达与EGFR激活和下游信号 (AKT,NFκB) 的增加相关.
- EGFR的α2,6化促进了其二分化和更高阶寡合化.
- EGFR化增强了细胞表面的受体循环和抑制了 lysosomal 降解,增加了与 Rab11 循环内体的共同定位,并减少了与 LAMP1 阳性 lysosomes 的共同定位.
结论:
- 通过ST6GAL1介导的EGFRα2,6化是一种促进卵巢癌EGFR信号传递的新机制.
- 这种化促进了EGFR的二聚化和寡聚化.
- 它还通过增强回收和减少退化来调节EGFR的贩运,从而有助于持续的信号传输.
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