奥斯托邦丁诱导了死结的癌细胞中的线粒体生物发生
Gulimirerouzi Fnu1, Georg F Weber1
1University of Cincinnati Academic Health Center, James L. Winkle College of Pharmacy, Cincinnati, OH 45229, USA.
Oncotarget
|December 1, 2023
概括
骨质丁-c通过通过CD44v和SLC7A11.11增加线粒体质量和ATP生成促进癌症转移. 这将短期新陈代谢与长期线粒体生物发生联系起来,提供新的治疗点.
科学领域:
- 癌症生物学 癌症生物学
- 代谢重编程 代谢重编程
- 线粒体功能的功能
背景情况:
- 与初级瘤相比,转移的癌细胞表现出不同的新陈代谢,具有显著的氧化酸化和ATP生成.
- 线粒体生物发生对于长期转移成功至关重要,但其与短期代谢变化的联系仍然不清楚.
- 已知骨质疏松素拼接变体可以增加死粘细胞中的ATP水平.
研究的目的:
- 研究癌症转移中的短期氧化代谢和长期线粒体生物发生之间的联系.
- 为了确定增加ATP的Osteopontin拼接变体是否也会诱导线粒体质量扩张.
- 阐明涉及Osteopontin介导的线粒体变化的信号通路及其在转移中的作用.
主要方法:
- 研究了奥斯托邦丁对转移细胞中的线粒体大小和质量的作用.
- 使用Osteopontin拼接变种 (-a和 -c) 来评估差异性影响.
- 研究了受体CD44v和载体SLC7A11在信号级联中的作用.
- 评估了PGC-1和过氧化物中间体的参与.
- 进行了*in vivo*实验,以评估抑制生物发生诱导机制对瘤质量的影响.
主要成果:
- 自克林骨质疏松素显著增加了线粒体大小,拼接变体-c比全长-a更强大.
- 骨质松丁-c通过其受体CD44v和SLC7A11.11的同结作用,调解这种作用.
- 信号通路涉及到线粒体生物发生诱导器PGC-1的激活.
- 过氧化物作为上游中间体,可能是由SLC7A11激活产生的.
- 在体内*抑制这些机制减少了扩散的瘤质量.
结论:
- 在癌症转移中,短期的氧化代谢和长期的线粒体生物发生之间存在功能联系,两者都由Osteopontin-c.
- 骨质丁-c通过CD44v/SLC7A11/PGC-1轴驱动线粒体生物发生,影响转移性进展.
- 这些发现揭示了潜在的治疗点,通过调节Osteopontin驱动的代谢适应来抑制癌症转移.
更多相关视频
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
18.7K
07:00Dual Effects of Melanoma Cell-derived Factors on Bone Marrow Adipocytes Differentiation
Published on: August 23, 2018
6.2K
相关概念视频
mTOR Signaling and Cancer Progression
3.8K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.8K
Mitochondria
13.3K
Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...
13.3K
Electron Transport Chain: Complex I and II
14.0K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
14.0K
PI3K/mTOR/AKT Signaling Pathway
3.6K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.6K
Adaptive Mechanisms in Cancer Cells
5.8K
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
5.8K
Metastasis
5.6K
Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
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...
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...
5.6K
