癌症干细胞对微环境线索的超反应性通过YAP/TAZ/TEAD控制转移和治疗反应
bioRxiv : the preprint server for biology
|June 26, 2025
概括
癌症干细胞 (CSCs) 通过自我更新驱动早期转移,然后转移到维护模式. 这些细胞作为瘤微环境的传感器,准YAP/TAZ通路可以逆转化疗诱导的CSC丰富.
科学领域:
- 癌症生物学 癌症生物学
- 转移研究 转移研究
- 干细胞生物学 干细胞生物学
背景情况:
- 癌症干细胞 (CSCs) 对转移和治疗耐药性至关重要.
- 在现场可视化和研究CSC是一个重大挑战.
研究的目的:
- 在转移殖民期间调查CSCs的种群动态.
- 了解微环境线索在CSC行为中的作用.
- 确定减少CSC丰富的治疗目标.
主要方法:
- 在乳腺癌模型中使用光CSC记者.
- 在肺殖民期间观察到CSC和非CSC种群动态.
- 对CSC对微环境线索的反应进行了机械分析.
- 研究了YAP/TAZ/TEAD路径的作用.
主要成果:
- CSCs通过扩展性自我更新驱动早期转移性病变的形成.
- 中央企业转向平衡的自我更新/差异化模式,非中央企业推动进一步扩张.
- CSC对像拥挤和营养物质这样的微环境线索反应过敏.
- 在YAP/TAZ/TEAD路径中介CSC对微环境信号的敏感性.
- 准YAP/TAZ输入逆转了化疗诱导的CSC丰富.
结论:
- 瘤核心细胞作为瘤微环境的传感器.
- 微环境线索通过YAP/TAZ调节CSC命运决策.
- 向YAP/TAZ通路提供了一种策略,以克服乳腺癌转移中的治疗阻力.
相关概念视频
Cancer Stem Cells and Tumor Maintenance
5.1K
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...
5.1K
Adaptive Mechanisms in Cancer Cells
5.9K
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,...
5.9K
The Tumor Microenvironment
6.8K
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
6.8K
Treatment Resistant Cancers
3.4K
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...
3.4K
Metastasis
5.7K
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...
5.7K
Mitogens and the Cell Cycle
7.0K
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...
7.0K


