RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Versatile function of NF-ĸB in inflammation and cancer.
Versatile function of NF-ĸB in inflammation and cancer.
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核因子-κB(NF-ĸB)在固有免疫和适应性免疫系统中均发挥关键作用,显著影响细胞增殖、迁移、分化、存活和干性等多种生理过程。NF-ĸB在癌症进展和化疗反应中的功能日益受到关注。本综述重点阐述NF-ĸB在炎症调控、生物学机制及癌症治疗中的治疗意义。NF-ĸB在改变TNF-α、IL-6和IL-1β等炎症因子释放方面起重要作用,这些因子是癌变调控的关键。
具体而言,在结肠炎等条件下,NF-ĸB上调可加剧炎症,可能导致结直肠癌的发生。其关键作用还延伸至调控肿瘤微环境,影响巨噬细胞、成纤维细胞、T细胞和NK 细胞等组分。这种调控影响肿瘤发生,并可削弱抗肿瘤免疫应答。
此外,NF-ĸB调节细胞死亡机制,尤其是通过抑制凋亡和铁死亡。它在多种癌症中还具有刺激或抑制自噬的双重作用。除上述功能外,NF-ĸB还参与调控癌症干细胞、促进血管生成、通过诱导EMT增加转移潜能,以及降低肿瘤细胞对化疗和放疗的敏感性。鉴于其致癌能力,研究已聚焦于能够抑制NF-ĸB的天然产物和小分子化合物,为癌症治疗提供了有前景的途径。
Nuclear factor-kappaB (NF-ĸB) plays a crucial role in both innate and adaptive immune systems, significantly influencing various physiological processes such as cell proliferation, migration, differentiation, survival, and stemness. The function of NF-ĸB in cancer progression and response to chemotherapy has gained increasing attention. This review highlights the role of NF-ĸB in inflammation control, biological mechanisms, and therapeutic implications in cancer treatment.
NF-ĸB is instrumental in altering the release of inflammatory factors such as TNF-α, IL-6, and IL-1β, which are key in the regulation of carcinogenesis. Specifically, in conditions including colitis, NF-ĸB upregulation can intensify inflammation, potentially leading to the development of colorectal cancer. Its pivotal role extends to regulating the tumor microenvironment, impacting components such as macrophages, fibroblasts, T cells, and natural killer cells. This regulation influences tumorigenesis and can dampen anti-tumor immune responses.
Additionally, NF-ĸB modulates cell death mechanisms, notably by inhibiting apoptosis and ferroptosis. It also has a dual role in stimulating or suppressing autophagy in various cancers.
Beyond these functions, NF-ĸB plays a role in controlling cancer stem cells, fostering angiogenesis, increasing metastatic potential through EMT induction, and reducing tumor cell sensitivity to chemotherapy and radiotherapy. Given its oncogenic capabilities, research has focused on natural products and small molecule compounds that can suppress NF-ĸB, offering promising avenues for cancer therapy.
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