L型氨基酸载体1 (LAT1) 通过在溶酶体的mTORC2激活促进PMA诱导的细胞迁移
Kun Tae1, Sun-Jick Kim1, Sang-Woo Cho1
1Department of Biological Sciences, Sungkyunkwan University, Suwon 16419, Republic of Korea.
Cells
|October 27, 2023
概括
L型氨基酸载体1 (LAT1) 在溶酶体上招募并激活mTORC2,促进细胞迁移. 这一发现为阻止癌症转移提供了潜在的治疗点.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 拉巴胺素 (mTOR) 途径的机械标调节细胞生长和新陈代谢.
- L型氨基酸载体1 (LAT1) 对于氨基酸运输和mTORC1激活至关重要.
- 在mTORC2调节和细胞迁移中LAT1的作用仍然在很大程度上未被探索.
研究的目的:
- 为了研究LAT1对mTORC2活性和 lysosomal局部化的影响.
- 阐明LAT1影响PMA诱导的细胞迁移的机制.
- 探索LAT1作为癌症中潜在的治疗点.
主要方法:
- 免疫光显微镜用于追踪LAT1和mTORC2的定位.
- 同免疫沉以评估LAT1-Rictor相互作用.
- 伤口愈合测试以评估细胞迁移.
- LAT1.1的遗传衰减和突变发生.
主要成果:
- 在PMA处理后,LAT1转移到溶解体,招募和激活mTORC2.2.
- lysosomal LAT1 与 Rictor 直接相互作用,Rictor 是 mTORC2.2. 的一个组成部分.
- LAT1 枯竭或特定的 LAT1 突变 (N3KR) 损害了 PMA 诱导的细胞迁移和 mTORC2 激活.
- 激活的mTORC2酸化物Akt,表示下游信号.
结论:
- lysosomal LAT1 是mTORC2激活和随后的细胞迁移的关键调节者.
- 在mTORC2信号传递中LAT1的作用为控制细胞运动提供了一个新的机制.
- 向LAT1可能提供一种治疗策略,以抑制癌症转移和进展.
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