NOX4通过癌细胞代谢重编程和CD8+T细胞抗瘤活性来调节乳腺癌的进展
Yingying Xiong1, Yiming Weng2, Shan Zhu3
1Department of Clinical Laboratory, Wuhan Fourth Hospital, Wuhan, China.
Frontiers in immunology
|February 24, 2025
概括
NADPH氧化酶4 (NOX4) 通过控制MYC驱动的新陈代谢和增强抗瘤免疫力来抑制侵袭性乳腺癌. 失去NOX4会使结果恶化,而其过度表达会改善存活率和免疫治疗反应.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 乳腺癌是全球女性死亡的主要原因之一.
- 在乳腺癌进展,新陈代谢和免疫反应中,NADPH氧化酶4 (NOX4) 的作用尚未完全理解.
研究的目的:
- 研究NOX4在乳腺癌攻击性,代谢重编程和免疫调节中的功能.
- 探索向NOX4-MYC轴和NOX4的免疫调节作用的治疗潜力.
主要方法:
- 在小鼠4T1和EO771乳腺癌模型中使用CRISPR/Cas9生成NOX4淘汰赛 (KO) 细胞系.
- 进行了体外和体内研究,包括代谢和转录组分析 (RNA测序).
- 研究了MYC的作用,描述了瘤透免疫细胞,并评估了与免疫治疗结合的NOX4过度表达.
主要成果:
- NOX4的删除加速了瘤的生长,增强了细胞的增殖和迁移,改变了细胞代谢 (增加了糖解和脂肪酸氧化).
- 失去NOX4导致MYC通路激活,减少CD8+T细胞透,增加PD-L1表达.
- NOX4过度表达改善了生存率,并与检查点阻塞免疫疗法协同作用.
结论:
- NOX4通过限制MYC驱动的代谢适应和支持抗瘤免疫力,在乳腺癌中起到瘤抑制作用.
- NOX4损失促进恶性瘤和免疫逃避,而NOX4过度表达提高了生存率和免疫疗法的有效性.
- 准NOX4-MYC轴和利用NOX4的免疫调节特性是乳腺癌的潜在治疗策略.
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
10:39Using Mouse Mammary Tumor Cells to Teach Core Biology Concepts: A Simple Lab Module
Published on: June 18, 2015
13.1K
相关概念视频
Inhibition of Cdk Activity
4.6K
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...
4.6K
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
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
Mitogens and the Cell Cycle
6.4K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.4K
Positive Regulator Molecules
105.7K
To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
105.7K
Metastasis
5.5K
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...
5.5K
