通过HSP90α/VCP-ERS/UPR轴,C1QL1可以抑制乳腺癌
Ningning Zhang1,2, Qing Shao1, Xinni Xiang3
1Department of Breast Cancer Center, Chongqing University Cancer Hospital, Chongqing, China.
Experimental & molecular medicine
|June 29, 2025
概括
补充成分1q域含蛋白1 (C1QL1) 作为乳腺癌 (BrCa) 瘤抑制剂. 通过促进物甲基化的沉默与预后不佳相关,而C1QL1重新表达通过诱导亡来抑制BrCa的进展.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 之前的研究发现,与正常组织相比,乳腺癌 (BrCa) 组织中的C1QL1表达较低.
- 在BrCa中C1QL1的生物学作用和分子机制在很大程度上仍未被描述.
研究的目的:
- 研究C1QL1在乳腺癌中的表达,甲基化状态和功能作用.
- 阐明C1QL1对BrCa细胞产生影响的分子通路.
主要方法:
- 基因表达分析 (RNA测序,qRT-PCR),蛋白质分析 (西方斑块,免疫组织化学) 和甲基化分析 (qMSP-PCR).
- 功能测定包括扩散 (CCK-8),细胞周期,细胞亡 (TUNEL),转移 (Transwell) 和体内异种移植模型.
- 蛋白质组分析 (LC-MS/MS) 和蛋白质相互作用研究 (co-IP,Western blot) 以确定相互作用的伙伴和途径.
主要成果:
- 由于促进物甲基化,C1QL1表达在BrCa中经常被沉默,较低的表达与更差的预后相关.
- 过度表达C1QL1抑制了BrCa细胞的增殖,迁移,以及在体外和体内诱导的亡.
- C1QL1与 HSP90α 和 VCP 相互作用,促进它们的降解,并触发ER压力/UPR介导的亡.
结论:
- 在乳腺癌中,C1QL1通过调节C1QL1/HSP90α/VCP-ERS/UPR通路,起到瘤抑制作用.
- C1QL1表达和其促进体甲基化状态可能作为BrCa.Ca的潜在诊断或预后生物标志物.
更多相关视频
08:48An In Vitro Dormancy Model of Estrogen-sensitive Breast Cancer in the Bone Marrow: A Tool for Molecular Mechanism Studies and Hypothesis Generation
Published on: June 30, 2015
8.3K
11:13Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment
Published on: June 9, 2023
1.7K
相关概念视频
Inhibition of Cdk Activity
4.9K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.9K
Anaphase Promoting Complex
3.0K
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
3.0K
Abnormal Proliferation
4.6K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.6K
The Intrinsic Apoptotic Pathway
6.9K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.9K
Receptor Downregulation in MVBs
2.2K
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...
2.2K
The Unfolded Protein Response
5.1K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
5.1K
