失去EGF受体极性使得上皮细胞模型中的恒温失衡成为可能
Cathleen R Carlin1,2, Syntyche Ngalula1
1Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, OH 44106-4970.
Molecular biology of the cell
|August 30, 2023
概括
在上皮细胞中错误准EGF受体 (EGFR) 破坏了极性,导致多层形成和维门丁上调等变化,模仿癌症的进展. 这突显了EGFR的两极性.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 皮质生物学 皮质生物学
背景情况:
- 像EGF受体 (EGFR) 一样,膜蛋白的极化分布对于上皮组织功能至关重要.
- EGFR对发育和恒温至关重要,其调节失调与癌症有关.
- 虽然EGFR通常局部化到底侧域,但它的排序可塑性是已知的,但域特异性基底仍然不太了解.
研究的目的:
- 为了研究错误向EGFR的影响,由于不活跃的基底侧排序信号,在上皮细胞对生长诱导的压力的恒温反应.
- 阐明特定信号通路在调解细胞对异常EGFR局部化的反应中的作用.
主要方法:
- 利用麦丁-达比犬 (MDCK) 细胞模型来研究EGFR误导.
- 分析了细胞反应,包括多层形成, anchorage-independent增长和维丁表达.
- 研究了Gab1-ERK5信号通路在整合压力反应中的作用.
主要成果:
- 异常的EGFR局部化,由不活跃的基底侧排序信号引起,诱导多层形成和独立于 anchorage的生长.
- 观察到维门的上调表达,维门是表皮细胞转变为介质细胞的标志物.
- 在顶内部化后,EGFRs被保留,Gab1-ERK5通路对于整合应激反应至关重要.
结论:
- 选择性EGFR错误向破坏了上皮细胞平衡,并促进了与癌症进展相关的表型.
- 该Gab1-ERK5信号通路在调解细胞对破坏EGFR极性反应方面发挥着关键作用.
- 控制EGFR极性的细胞机械在与恒温不平衡相关的上皮病理中很重要.
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