独特的共享和区间丰富的致癌网络推动了原发性与转移性乳腺癌的发展
Zhe Jiang1, YoungJun Ju1, Amjad Ali1
1Toronto General Research Institute - University Health Network, 101 College Street, Max Bell Research Centre, suite 5R406, Toronto, ON, M5G 1L7, Canada.
Nature communications
|July 18, 2023
概括
了解乳腺癌转移驱动因素是关键. 这项研究确定了初级瘤与转移中的共享和独特的瘤性途径,揭示了防止传播的新治疗点.
科学领域:
- 在瘤学瘤学.
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
背景情况:
- 转移性乳腺癌仍然是全球癌症死亡的主要原因.
- 促进原发性瘤生长与转移的特定遗传驱动因素尚未完全理解.
- 视网母细胞瘤1 (RB1) 在乳腺癌中经常被禁用,但其在转移中的作用仍在争论中.
研究的目的:
- 调查原发性乳腺瘤和转移的独特和共同的致癌驱动因素.
- 确定预防乳腺癌转移的潜在治疗点.
- 为了将小鼠模型的发现与人类临床数据相关联.
主要方法:
- 在雌性小鼠中对哺乳动物特异性转体子突变发生的选.
- 包括功能丧失的Rb突变来模拟乳腺癌.
- 在初级瘤和转移中分析基因中心的常见插入部位 (gCIS).
- 分析了四个人类临床队列的途径分析,其中主要瘤和转移结合在一起.
主要成果:
- 识别了在原发性瘤,转移或两者中丰富的独特基因组.
- 发现了一种MET-RAS网络,这种网络在原发性瘤和转移中都很常见.
- 发现了转移特定的信号枢纽,包括Rho信号,Ubiquitination和RNA处理.
- 人类数据证实了亚型特定的驱动因素,具有共享的 (如RB1,TP53,MET,RAS),初级丰富的 (如EGFR,TGFβ,STAT3) 和转移丰富的 (如RHO,PI3K) 途径.
- 针对RB1缺陷或MET/RHO信号的抑制剂在阻断迁移和诱导细胞死亡方面表现出协同作用.
结论:
- 乳腺癌转移是由一组独特的瘤信号通路驱动的,与驱动主要瘤生长的信号通路分开.
- 针对共享的瘤驱动因素 (MET-RAS) 和转移特异性驱动因素 (Rho信号) 提供了一个有前途的策略来预防或治疗转移性乳腺癌.
- 治疗策略应区分原发性瘤生长的驱动因素和促进转移的驱动因素,以获得最佳的疗效.
相关概念视频
02:30Metastasis
5.6K
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...
5.6K
02:07Tumor Progression
6.4K
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...
6.4K
02:53Adaptive Mechanisms in Cancer Cells
5.8K
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,...
5.8K
02:26Protein Networks
4.0K
An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
4.0K
02:21Cancers Originate from Somatic Mutations in a Single Cell
12.1K
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...
12.1K
02:40Cancer Stem Cells and Tumor Maintenance
5.0K
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...
5.0K