阻断CXCR4-CARM1-YAP轴可以通过抑制有氧糖解来克服骨髓瘤对多克索鲁比的抗性
Zihua Li1,2, Hengli Lu1, Yiwei Zhang1
1Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Cancer science
|July 29, 2024
概括
这项研究揭示了CXCR4和CARM1信号如何通过控制有氧糖解来驱动骨肉瘤中的多克索鲁比辛耐药性. 针对这一轴可以克服耐药性并改善治疗结果.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症新陈代谢 癌症新陈代谢
背景情况:
- 骨髓瘤具有攻击性,并且通常对化疗,特别是多克索鲁比辛,具有耐药性.
- 骨髓瘤中多克索鲁比辛耐药性是一个主要的临床挑战.
- 有氧糖解与化学抵抗有关.
研究的目的:
- 在 doxorubicin 耐药性中研究 CXCR4-CARM1-YAP 信号轴.
- 阐明这个轴在调节有氧糖解中的作用.
- 确定潜在的治疗点,以克服药物耐药性.
主要方法:
- 基因沉默和多克索鲁比治疗骨髓瘤细胞.
- 海马对有氧糖解的测定.
- RNA测序和免疫光染色.
- 染色体免疫沉 (ChIP) 和体内异种移植模型.
主要成果:
- 在抗多克索鲁比细胞中发现了CXCR4的过度表达.
- 破坏CXCR4对多克索鲁比敏感的细胞和改变的葡萄糖分解.
- CARM1调节糖解,在耐药瘤中过度表达.
- 在H3R17的CARM1甲基化影响了YAP表达;在体内,CARM1过度表达抵消了CXCR4抑制效应.
结论:
- CXCR4-CARM1-YAP轴对氧化糖解和骨髓瘤中多克索鲁比辛耐药性至关重要.
- 针对这种代谢和信号网络提供了一个潜在的治疗策略.
- 这些发现为改善骨髓瘤治疗结果提供了洞察力.
更多相关视频
相关概念视频
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
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
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
Targeted Cancer Therapies
7.5K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
There are several types of targeted therapies against...
7.5K
Cancer Therapies
7.6K
Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
7.6K


