伴侣介导的自调节了中介细胞瘤的转移状态
Xun Zhou1, Eva Berenger1, Yong Shi1
1Department of Physiology and Pharmacology, Karolinska Institutet, 171 65, Stockholm, Sweden.
EMBO molecular medicine
|March 7, 2025
概括
由LAMP-2A淘汰引起的Chaperone介导的自 (CMA) 缺乏,增强了癌症的攻击性和转移. 在转移性病变中抑制LAMP-2A表明CMA.
科学领域:
- 癌症生物学 癌症生物学
- 细胞机制 细胞机制
- 分子瘤学分子瘤学
背景情况:
- 瘤通过特定的蛋白质稳定获得侵入性和传播能力.
- 蛋白质降解失败在癌症转移中的作用尚不清楚.
- 伴奏介导自 (CMA) 是一种关键的蛋白质降解途径.
研究的目的:
- 为了研究LAMP-2A缺乏对癌症攻击性和转移的影响.
- 阐明CMA,TGFβ信号传递和上皮-介质细胞转换 (EMT) 之间的机械联系.
- 确定LAMP-2A表达在转移性癌症中的临床相关性.
主要方法:
- 产生的人类癌细胞特异性淘汰 (KO) 的LAMP-2A.
- 在体内评估瘤细胞的扩散,入侵和转移.
- 在临床原发性和转移性瘤样本中分析了LAMP-2A表达.
- 研究了CMA,TGFβ信号传递和EMT相关蛋白质 (例如TGFβR2) 之间的相互作用.
主要成果:
- LAMP-2A KO促进了细胞间瘤的攻击性,导致广泛传播和转移.
- 与原发性瘤相比,转移性病变表现出抑制的LAMP-2A表达.
- CMA缺乏症加剧了TGFβ信号传递,而TGFβ抑制抑制了瘤生长.
- CMA降解了像TGFβR2.2这样的EMT驱动蛋白.
结论:
- 通过LAMP-2A,CMA通过负调节TGFβ驱动的EMT作为瘤抑制剂起作用.
- 缺乏CMA有助于癌细胞的侵入性和转移.
- 癌症患者的LAMP-2A表达水平与转移潜力相关.
相关概念视频
mTOR Signaling and Cancer Progression
3.7K
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...
3.7K
Autophagy
4.1K
Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
4.1K
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
Receptor Downregulation in MVBs
2.0K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.0K
Delivery Pathways to the Lysosome
6.1K
Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
6.1K
Regulation of Nuclear Protein Sorting
2.3K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.3K


