细胞状态过渡模型对乳腺癌细胞表型进行分层,并揭示新的治疗点
Oleksii S Rukhlenko1, Hiroaki Imoto1, Ayush Tambde1,2
1Systems Biology Ireland, School of Medicine, University College Dublin, D04 V1W8 Dublin, Ireland.
Cancers
|July 13, 2024
概括
一种新的细胞状态转变评估和调节 (cSTAR) 方法揭示了乳腺癌 (BC) 亚型中的关键信号驱动因素. 这些发现使数字细胞双胞胎能够控制细胞表型,并建议有针对性的抑制策略.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 系统生物学 系统生物学
背景情况:
- 了解细胞信号和表型控制在生物学中至关重要.
- 乳腺癌 (BC) 亚型表现出复杂的信号模式.
- 蛋白质组数据为细胞状态提供了洞察力.
研究的目的:
- 应用一种新的细胞状态转变评估和调控 (cSTAR) 方法来分析乳腺癌细胞系的蛋白质组数据.
- 识别不同BC亚型和正常细胞的核心信号网络,因果关系和瘤驱动因素.
- 开发用于控制细胞状态转换的机制模型.
主要方法:
- 应用细胞状态转变评估和调控 (cSTAR) 方法对来自乳腺癌和正常细胞系的单细胞蛋白质组数据.
- 细胞状态的分离为光线,基底和正常类别.
- 识别和分析信号节点,网络拓和因果关系.
主要成果:
- 在光BC细胞中确定了保存的核心网络架构,mTOR作为关键驱动器.
- 在基底BC细胞中发现了异质的核心网络,将其分为具有不同的驱动因素的四个子类.
- 在正常的乳腺组织细胞中特征了两个子类.
- 开发了代表数字细胞双胞胎的机械cSTAR模型.
结论:
- cSTAR方法有效地将信号驱动器和网络架构划分为BC子类型.
- 机械cSTAR模型为理解和控制细胞状态转换提供了一个框架.
- 这项研究表明,潜在的治疗策略包括小分子抑制剂,以使BC细胞中的酸化网络正常化.
更多相关视频
08:48An In Vitro Dormancy Model of Estrogen-sensitive Breast Cancer in the Bone Marrow: A Tool for Molecular Mechanism Studies and Hypothesis Generation
Published on: June 30, 2015
8.2K
07:03Isolation and Functional Assessment of Human Breast Cancer Stem Cells from Cell and Tissue Samples
Published on: October 2, 2020
4.5K
相关概念视频
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
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
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
Tumor Progression
6.3K
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
6.3K
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
