通过CYRI-B介导的巨细胞酶会通过溶酸酸受体吸收驱动转移
Savvas Nikolaou1, Amelie Juin1, Jamie A Whitelaw1
1CRUK Scotland Institute, Switchback Road, Bearsden, Glasgow, United Kingdom.
eLife
|May 7, 2024
概括
CYRI-B蛋白影响胰腺癌的进展. 虽然它的缺席加速了早期瘤的生长,但它通过损害关键信号受体的吸收来抑制转移,提供了新的治疗点.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 胰腺管腺癌 (PDAC) 的预后不佳,治疗方法有限.
- 克拉斯的过度活化驱动瘤细胞迁移,增殖和巨细胞.
- 巨细胞在信号受体贩运中的作用尚不清楚.
研究的目的:
- 研究CYRI-B在KRAS驱动的胰腺癌中的作用.
- 了解CYRI-B在瘤生长和转移中的作用.
- 探索CYRI-B对RAC1激活和信号通路的影响.
主要方法:
- 利用KRAS和p53驱动的胰腺癌的小鼠模型.
- 在野生型和Cyrib缺乏的小鼠中评估瘤生长和转移.
- 分析了细胞的增殖,迁移和巨细胞.
- 量化 lysophosphatidic 酸受体 1 (LPA1) 在 CYRI-B 枯竭细胞的吸收.
主要成果:
- 在胰腺瘤中,CYRI-B的表达很高.
- 删除Cyrib可以通过增强ERK和JNK信号来加速早期瘤形成.
- 在疾病的后期阶段,CYRI-B的丧失抑制了转移.
- 由于LPA1.1的宏皮诺细胞吸收受损,CYRI-B的耗尽减少了向酸酸的化学作用.
结论:
- 在早期胰腺癌中,CYRI-B作为RAC1过活化的缓冲剂.
- CYRI-B调解瘤细胞的生长和信号传递.
- 在胰腺癌中,CYRI-B具有双重作用,促进早期生长,但抑制后期转移.
- 向CYRI-B介导的巨细胞瘤提供了胰腺癌的潜在治疗策略.
相关概念视频
Metastasis
5.5K
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...
5.5K
Cancer Cell Migration through Invadopodia
2.3K
Invadosome is a broad category of cell surface structures with proteolytic activity that degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
2.3K
mTOR Signaling and Cancer Progression
3.8K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.8K
IP3/DAG Signaling Pathway
12.0K
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
12.0K
Receptor-mediated Endocytosis
104.4K
Overview
104.4K
Pinocytosis
3.3K
Cells use energy-requiring bulk transport mechanisms to transfer large particles or large numbers of small particles into or out of the cell. The cells envelop the particles in spherical membranes called vesicles or vacuoles. Vesicles that transport material into the cell are built from the cell membrane. These vesicles encapsulate external molecules and transport them into the cell in a process called endocytosis.
Pinocytosis ("cellular drinking") is one of three main types of...
Pinocytosis ("cellular drinking") is one of three main types of...
3.3K


