瘤再生细胞通过PCK2-依赖的脂重塑来逃避铁亡
Zhe Li1,2,3, Zhi-Min Xu1,2,3, Wei-Peng Chen1,2
1State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
Nature chemical biology
|May 8, 2024
概括
类似干细胞的癌细胞通过降低铁灭的敏感性来抵抗治疗. 这涉及PCK2-ACSL4通路,较高的PCK2和pACSL4水平与鼻癌的更好的治疗反应相关.
科学领域:
- 癌症生物学 癌症生物学
- 细胞的新陈代谢
- 在瘤学瘤学.
背景情况:
- 干细胞样癌细胞 (TRCs) 与治疗耐药性有关.
- 铁灭脱离在TRC介导的耐药性中的作用尚未完全理解.
研究的目的:
- 为了研究干细胞类癌细胞是否逃避铁灭,从而引起治疗耐药性.
- 阐明TRCs中ferroptosis逃避背后的分子机制.
主要方法:
- 利用软纤维素凝培养系统研究瘤再生细胞 (TRCs).
- 采用了定量质谱和脂质组分析.
- 研究了线粒体代谢激酶PCK2和ACSL4在铁亡中的作用.
主要成果:
- TRCs表现出降低铁灭的敏感性,有助于化疗和放射治疗的耐药性.
- 线粒体激酶PCK2酸化并激活ACSL4,驱动铁化相关的脂重塑.
- TRCs降低了PCK2表达的调节,建立了耐铁的状态.
- 较高的PCK2和酸化ACSL4 (pACSL4(T679) 水平与改善治疗反应和减少鼻癌转移相关.
结论:
- 通过PCK2介导的ACSL4激活是癌细胞中ferroptosis调节的关键机制.
- 准PCK2-pACSL4通路可能为克服化疗和放射电阻提供新的治疗策略.
- 生物标志物PCK2和pACSL4 (T679) 显示出预测鼻癌治疗结果的潜力.
相关概念视频
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
Cancer Stem Cells and Tumor Maintenance
4.9K
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...
4.9K
Adaptive Mechanisms in Cancer Cells
5.7K
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,...
5.7K
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
Treatment Resistant Cancers
3.3K
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.3K
Necrosis
4.5K
Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
4.5K


