非正规EGFR信号传递促进了MAPK依赖的上皮细胞挤出
Paola Molina1, Mikiyas Daniel1, Tung Hoang1
1Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville TN 37205, USA.
Journal of cell science
|October 24, 2025
概括
瘤基因诱导的细胞挤出,癌症机制,意外地需要表皮生长因子受体 (EGFR) 信号. 这种EGFR通路影响E-cadherin的内部化,影响表皮单层中的细胞挤出.
科学领域:
- 细胞生物学 细胞生物学
- 癌症生物学 癌症生物学
- 分子瘤学分子瘤学
背景情况:
- 瘤基因诱导的上皮细胞挤出是一种已知的现象,但其确切的机制尚不清楚.
- 了解细胞挤出对于理解瘤抑制和癌症进展动态至关重要.
研究的目的:
- 调查瘤性Ras诱导的上皮细胞挤出背后的分子机制.
- 阐明表皮生长因子受体 (EGFR) 在这种挤出过程中的信号传导作用.
主要方法:
- 使用乳腺上皮细胞单层与诱导的瘤性Ras (Q61L).
- 评估了ERK酸化,AKT激活和EGFR信号传递 (使用erlotinib和基因删除) 的要求.
- 研究了对Ras-GTP水平,ERK酸化,SOS1/2,MEK激活和E-cadherin内部化的影响.
主要成果:
- 拉斯依赖细胞挤出需要ERK酸化,但不需要AKT激活.
- 在Ras表达细胞中,EGFR抑制和EGFR删除意外地抑制了挤出.
- EGFR抑制减少了由构成性活性MEK驱动的挤出,并部分阻止了E-cadherin内部化.
结论:
- EGFR信号传递在瘤基因诱导的上皮细胞挤出中起着非正规的作用.
- EGFR信号传递可能会通过促进E-cadherin内细胞分裂来调解细胞挤出.
- 这些发现揭示了EGFR参与癌细胞行为的新方面.
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