PDIA3驱动的STAT3/PD-1信号促进M2 TAM两极分化,并加剧结直肠癌的进展
Jianchun Fan1, Likun Wang2, Chunze Zhang3
1Graduate School, Hebei North University, Zhangjiakou 075000, China.
Aging
|May 18, 2024
概括
蛋白脱硫化异构酶A3 (PDIA3) 通过增强瘤相关的巨细胞,促进结直肠癌的生长. 通过PD-1阻断准PDIA3,为结直肠癌提供了一个新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 瘤相关巨细胞 (TAMs) 在结直肠癌的进展中发挥着关键作用.
- 通过TAMs影响结直肠癌发生的精确分子机制尚未完全理解.
研究的目的:
- 调查蛋白脱硫化异构酶A3 (PDIA3) 在调节结直肠癌中瘤相关的巨细胞中的作用.
- 阐明涉及PDIA3介导结直肠瘤发生的潜在生化途径.
主要方法:
- 在癌症数据集中对PDIA3,STAT3和CD274表达的生物信息学分析.
- 在免疫缺陷小鼠中的异种移植模型评估PDIA3对结直肠癌的影响.
- 西部斑点分析用于量化蛋白质表达 (PDIA3,p-STAT3,PD-1,XBP-1,IL-6).
- 在体外测试评估SW480细胞迁移,入侵和增殖.
主要成果:
- 在结肠直肠癌中,PDIA3的调节升高,并且与STAT3和CD274表达具有正相关性.
- 在SW480细胞中PDIA3的过度表达增加了瘤性和瘤性行为.
- 干预PD-1单克隆抗体减少了PDIA3驱动的瘤生长.
- 通过STAT3/PD-1通路,PDIA3增强了TAMs的M2极化.
结论:
- 通过STAT3/PD-1信号通路调节TAMs,PDIA3促进结直肠癌的进展.
- 在结直肠癌治疗中,PDIA3代表了PD-1阻断的潜在治疗标.
更多相关视频
相关概念视频
Abnormal Proliferation
4.5K
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...
4.5K
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
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
The JAK-STAT Signaling Pathway
8.8K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
8.8K
Tumor Progression
6.3K
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...
6.3K
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


