口服CSC中缺氧诱导的代谢和功能变化:通过BNIP3驱动的线粒调节的干部和活性的影响
Xin Li1, Hitesh Singh Chaouhan1, Shao-Hua Yu2
1Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
Journal of cellular and molecular medicine
|February 13, 2025
概括
口腔瘤中的癌症干细胞 (CSC) 通过BNIP3驱动的自生存下来,增强它们的干细胞性并促进转移. 抑制BNIP3和自为口腔状细胞癌提供了潜在的治疗策略.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 癌症干细胞研究研究
背景情况:
- 口腔状细胞癌 (OSCCs) 携带癌症干细胞 (CSCs),对于转移和在缺氧等压力下生存至关重要.
- 在低氧条件下使CSC生存的分子机制在很大程度上是未知的.
研究的目的:
- 调查自在口服中枢神经细胞维护和低氧压力下生存中的作用.
- 阐明参与CSC适应缺氧的特定途径.
主要方法:
- 在不同的缺氧条件下培养人类OSCC细胞系 (OECM-1和OECM-1 CSCs).
- 通过球体形成,穿孔和伤口愈合测试来评估CSC茎状性质.
- 分析了线粒体功能,线粒体和代谢途径 (糖分解,OXPHOS) 使用西方抹杀,IHC和XF-海马试验.
- 检查了BNIP3/-L沉默对CSC干度的影响.
主要成果:
- 缺氧增加了与OECM-1细胞相比,在口腔CSC中增加了增殖,入侵,迁移和上皮细胞转移到介质细胞 (EMT).
- 缺氧诱导的BNIP3驱动的线粒在OECM-1 CSC中被上调,与对氧化酸化 (OXPHOS) 的代谢转变相关.
- 沉默BNIP3/-L显著降低了OECM-1 CSC的干性特征.
- TCGA数据显示,在头部和部状细胞癌瘤中,BNIP3表达较高,与患者存活率较低有关.
结论:
- BNIP3/L驱动的自对于在缺氧状态下维持口腔中枢神经干是必不可少的.
- 这一途径促进了对低氧的代谢适应,支持CSC生存和侵略性表型.
- 针对BNIP3和自是一种有希望的治疗途径,用于口腔CSCs.
相关概念视频
02:53Adaptive Mechanisms in Cancer Cells
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,...
01:19Multipotency of Hematopoietic Stem Cells
The hematopoietic stem cells or HSCs are multipotent, meaning they can differentiate and give rise to all blood and immune cells. HSCs are maintained in the quiescent stage until an external stimulus initiates their differentiation. The multipotent HSCs exist as two heterogeneous populations, long-term repopulating cells (LTRC) and short-term repopulating cells (STRC). The two HSC populations have different surface markers or receptors and are classified based on quiescence and long-term...
01:01Regulation of Hematopoietic Stem Cells
All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
01:26Stem Cell Niche
The stem cell niche is the dynamic microenvironment where stem cells reside. Inside these niches, the cells may remain undifferentiated, undergo high self-renewal, or become lineage-specific progenitors. Stem cells coexist with other niche cells, such as stromal cells. They also interact closely with the ECM. Cell-cell and cell-matrix communication occur via adhesion molecules or soluble factors that signal the stem cells and determine their fate. Stromal cells also provide survival signals to...