通过增加铜水平和压力激活的MAP激酶活性,STEAP2促进肝细胞癌的进展
Carla Zeballos Torrez1, Acarizia Easley1, Hakim Bouamar1
1Department of Cell Systems and Anatomy, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Scientific reports
|June 3, 2024
概括
前列腺的六种跨膜上皮抗原2 (STEAP2) 通过增加铜水平和激活MAP激酶,推动细胞迁移和入侵,促进肝细胞癌 (HCC) 恶性病. 这项研究确定了STEAP2作为HCC治疗的潜在治疗标.
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:
- 前列腺的六种跨膜上皮抗原2 (STEAP2) 是一种参与金属离子吸收的金属还原酶.
- STEAP2在肝细胞癌 (HCC) 发病过程中的特定作用尚不清楚.
研究的目的:
- 研究STEAP2在HCC进展中的作用和分子机制.
- 评估STEAP2作为HCC的潜在治疗点.
主要方法:
- 用RNA测序,RT-qPCR,西式涂抹和免疫染色来评估HCC组织和细胞系中的STEAP2表达.
- 为了研究其在体外和体外的功能效应,进行了STEAP2的淘汰和过度表达.
- 进行了基因表达,细胞迁移,侵袭,细胞内铜水平和MAP激酶激活 (p38,JNK) 的分析.
主要成果:
- 在HCC瘤中,STEAP2表达显著上调,并与较高的瘤等级相关.
- STEAP2敲除废除了HCC细胞恶性表型,抑制了迁移和入侵.
- STEAP2敲击降低了细胞内铜水平和MAP激酶激活;铜补充物挽救了迁移缺陷.
结论:
- 通过增加铜吸收和MAP激酶信号传导,STEAP2通过增强细胞迁移和侵入来促进HCC恶性病变.
- STEAP2代表了一种新的分子机制,有助于HCC的进展和潜在的治疗点.
相关概念视频
MAPK Signaling Cascades
5.4K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.4K
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
Interactions Between Signaling Pathways
6.3K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.3K
PI3K/mTOR/AKT Signaling Pathway
3.5K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.5K
Psychoneuroimmunology: Diabetes and Cancer
28
Chronic stress has been linked to both the onset and progression of serious health conditions, including Type 2 diabetes and cancer. Type 2 diabetes, a widespread chronic illness, is closely associated with obesity and insulin resistance, both of which often worsen under stress. Studies indicate that men experiencing high levels of chronic stress face a 45% higher risk of developing diabetes compared to those with minimal stress. Stress triggers physiological responses that elevate blood...
28
Cell Specific Gene Expression
13.6K
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
13.6K


