线粒体Ca2+通过调节上皮细胞可塑性来控制胰腺癌的生长和转移
Jillian S Weissenrieder1, Jessica Peura2,3, Usha Paudel1
1Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
通过线粒体单载体 (MCU) 摄取线粒体的过程驱动胰腺癌的生长和转移. 抑制MCU可以通过阻断癌细胞可塑性和上皮细胞转移到介质细胞转变 (EMT) 来减少瘤的进展和扩散.
科学领域:
- 细胞生物学 细胞生物学
- 在瘤学瘤学.
- 生物化学 生物化学
背景情况:
- 细胞内膜网膜到线粒体的转移对于癌细胞的生存至关重要.
- 在胰腺腺癌 (PDAC) 中,通过线粒体单携体 (MCU) 摄取线粒体的作用尚不清楚.
研究的目的:
- 调查MCU在胰腺腺癌 (PDAC) 进展和转移中的作用.
- 确定MCU是否是PDAC的潜在治疗点.
主要方法:
- 在PDAC患者样本中评估了MCU表达.
- 使用具有MCU删除 (Mcu KO) 的同位素小鼠PDAC模型.
- 评估了MCU删除后的瘤细胞增殖,自我更新和转移.
主要成果:
- 增加的MCU表达与PDAC恶性瘤和患者的不良结果相关.
- 在小鼠模型中Mcu删除减少了增殖,自我更新和转移.
- 通过减少牛的表达和TGFβ分泌,Mcu删除抑制了表皮细胞到介质细胞的过渡 (EMT).
- 恢复牛或TGFβ挽救了Mcu KO细胞中的转移性缺陷.
结论:
- 通过MCU介导的线粒体摄取对于PDAC细胞增殖,可塑性和转移至关重要.
- 向MCU可能是一个可行的治疗策略,以抑制EMT和PDAC中的转移.
更多相关视频
08:16Mimicking and Manipulating Pancreatic Acinar-to-Ductal Metaplasia in 3-dimensional Cell Culture
Published on: February 11, 2019
19:44Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen
Published on: May 30, 2012
相关概念视频
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Adaptive Mechanisms in Cancer Cells
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Electron Transport Chain: Complex I and II
ROS generation is regulated and maintained at moderate levels necessary...
Metastasis
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
Mitochondrial Membranes
Mitogens and the Cell Cycle
