通过CPT1A介导的MFF化促进了卵巢癌干细胞的干细胞维护
Yaqin Zhu1, Shuting Chen1, Hong Su1
1College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi, China.
Communications biology
|February 16, 2025
概括
卡尼丁棕转移酶1A (CPT1A) 通过调节脂质脱,维持卵巢癌干细胞 (OCSC) 的干性. 抑制CPT1A的活性为卵巢癌提供了潜在的治疗策略.
科学领域:
- 生物化学 生物化学
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
背景情况:
- 癌症干细胞 (CSCs) 驱动瘤的进展,转移和治疗抵抗.
- 了解CSC维持机制对于开发有效的癌症疗法至关重要.
- 卵巢癌干细胞 (OCSCs) 是克服治疗失败的关键目标.
研究的目的:
- 调查卡尼丁棕转移酶1A (CPT1A) 在维持OCSC干性的作用.
- 阐明CPT1A调节OCSC属性的分子机制.
- 评估CPT1A作为卵巢癌的潜在治疗标.
主要方法:
- 在OCSCs中对CPT1A表达的定量分析.
- 研究CPT1A对脂质代谢和SREBP1/SCD1通路的影响.
- 关于CPT1A介导的线粒体裂变因子 (MFF) 的机制研究.
- 在体外和体内实验中使用格利布里德抑制CPT1A活性并评估抗瘤作用.
主要成果:
- 在OCSC中,CPT1A的表达很高,对维持其干性至关重要.
- 通过增强SREBP1激活和SCD1表达,CPT1A促进了脂质脱.
- CPT1A表现出氨酸糖转移酶 (LSTase) 活性,促进MFF糖和SREBP1激活.
- 用GLYBURIDE抑制CPT1A的LSTase活性,可以降低OCSC的干度,并增强西斯普拉丁的疗效.
结论:
- CPT1A的LSTase活性对于维持OCSC干和脂质代谢至关重要.
- 准CPT1A的酶功能为卵巢癌提供了一个新的治疗途径.
- 抑制CPT1A显示了在卵巢癌治疗中增强常规化疗的潜力.
相关概念视频
Cancer Stem Cells and Tumor Maintenance
4.7K
Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
4.7K
mTOR Signaling and Cancer Progression
3.7K
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...
3.7K
Abnormal Proliferation
4.4K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.4K
Maintenance of the ES Cell State
2.1K
The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...
2.1K
Induced Pluripotent Stem Cells
3.9K
Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
Somatic...
3.9K
Stem Cell Niche
5.0K
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...
5.0K


