克隆进化和转录性可塑性塑造了前列腺癌中转移性传播路径
Migle Mikutenaite1,2, Evdoxia Karadoulama1,2, Francesco Favero1,2
1The Finsen Laboratory, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Nature communications
|December 23, 2025
概括
前列腺癌以克隆方式发展,遗传和细胞变化导致转移. 了解这种相互作用为更好的患者护理提供了新的预后标记.
科学领域:
- 在瘤学瘤学.
- 基因组学就是基因组学.
- 文字转录学 (Transcriptomics) 是一个学科.
背景情况:
- 前列腺癌由于基因组和转录性改变而表现出显著的异质性.
- 克隆进化,细胞可塑性和转移中的瘤微环境之间的关系尚不清楚.
研究的目的:
- 为了重建克隆进化和转录变化驱动前列腺癌转移在单细胞分辨率.
- 研究转移性前列腺癌中基因组变化和转录性可塑性之间的相互作用.
主要方法:
- 单核RNA测序和全基因组测序的整合.
- 分析了来自当地晚期前列腺癌的5名患者的43个空间明显的瘤样本.
主要成果:
- 确定了广泛的克隆异质性,具有单基因和多基因转移性传播.
- 在转移后的初级瘤中观察到正在进行的克隆进化.
- 发现的转移性播种趋于涉及基因组和转录变化的轨迹,包括雄激素受体独立性和雌激素,WNT和JAK-STAT通路的激活.
结论:
- 前列腺癌转移是由克隆进化和细胞可塑性之间的复杂相互作用驱动的.
- 研究结果表明,可能需要更具整合性的预后标志物来改善患者管理.
相关概念视频
Metastasis
6.3K
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...
6.3K
Tumor Progression
7.2K
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...
7.2K
Adaptive Mechanisms in Cancer Cells
6.9K
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,...
6.9K
Chemotaxis and Direction of Cell Migration
4.3K
Cells can detect chemical cues in their environment and reorganize the cytoskeleton to migrate toward them or away from them. This directional migration, called chemotaxis, is essential during embryogenesis and development, immune response, tissue repair and regeneration, and reproduction. These chemical cues can either attract or repel the cell's movement. For example, axon development is determined by a combination of chemoattractants and chemorepellents that direct the growing axon...
4.3K
Cancers Originate from Somatic Mutations in a Single Cell
14.5K
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
14.5K
Cancer Stem Cells and Tumor Maintenance
5.8K
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...
5.8K


