PPP2CA抑制通过AMPK/SCD1通路促进结肠直肠癌中的铁灭敏感性
Xiaojie Liang1, Hui Zhang1, Weiwei Shang1
1Department of General Surgery, The Affiliated Jiangning Hospital of Nanjing Medical University, 169 Hushan Road, Nanjing, 211100, China.
Digestive diseases and sciences
|April 18, 2024
概括
向PPP2CA通过增加氧化应激和脂质过氧化,增强结直肠癌 (CRC) 细胞中的铁亡. 这表明PPP2CA是CRC治疗的潜在治疗标.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 结肠直肠癌 (CRC) 仍然是一个重大的健康挑战,尽管目前的治疗方法,死亡率很高.
- 蛋白质酸化对癌症的发展和进展至关重要.
- 铁亡,一种独特的编程细胞死亡形式,与包括癌症在内的各种疾病有关.
研究的目的:
- 调查蛋白质酸酶2催化子单元α (PPP2CA) 在结直肠癌 (CRC) 进展中的作用.
- 为了确定PPP2CA是否影响CRC细胞中埃拉斯诱导的铁亡.
主要方法:
- 在HCT116CRC细胞中抑制PPP2CA,以评估其对恶性表型和铁亡的作用.
- 测量马隆迪甲基 (MDA),活性氧物种 (ROS),Fe2+和GSH/GSSG比率以评估铁.
- 分析SCD1表达及其通过AMPK信号通路的调节.
主要成果:
- 抑制PPP2CA显著增强了HCT116细胞的恶性表型.
- PPP2CA的淘汰会增强埃拉斯诱导的铁,由增加的MDA,ROS,Fe2+和降低的GSH/GSSG比率证明.
- 抑制PPP2CA导致通过AMPK依赖机制在CRC细胞中减少SCD1的表达.
结论:
- PPP2CA在调节结直肠癌进展方面发挥着至关重要的作用.
- 通过AMPK/SCD1信号通路,PPP2CA抑制增强了埃拉斯诱导的铁亡.
- 针对PPP2CA代表了CRC的潜在治疗策略.
相关概念视频
PI3K/mTOR/AKT Signaling Pathway
3.5K
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...
3.5K
Abnormal Proliferation
4.5K
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...
4.5K
Interactions Between Signaling Pathways
6.3K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.3K
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
Electron Transport Chain: Complex I and II
13.1K
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...
13.1K
Inhibition of Cdk Activity
4.7K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.7K


