TNF-α, and TNFRs in gastrointestinal cancers

IF 2.9 4区 医学 Q2 PATHOLOGY Pathology, research and practice Pub Date : 2024-10-17 DOI:10.1016/j.prp.2024.155665
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Abstract

Tumor necrosis factor-alpha (TNF-α) is a multifunctional cytokine that plays a role in the hemostasis of the immune system, inflammation, and cell proliferation. However, it can also have a dark side as it is involved in pro-inflammatory cytokines and pathological processes such as cell growth and death, autoimmunity, and inflammation, leading to a wide range of chronic inflammatory diseases, including digestive cancer. TNF-alpha binds to two distinct receptors, TNFRI and TNFRII. Upon binding of the ligand to these receptors, TNF receptor-associated factors (TRAFs) are recruited to the cytoplasmic receptor, triggering the activation of transcription factors such as NF-kB and Activator protein 1 (AP_1). In contrast, binding of cytokines to certain family members, such as TNF RI and Fas Ligand (Fas L), leads to the secretion and initiation of apoptosis. Gastrointestinal malignancies are among the most common types of cancer globally. Despite extensive research, the exact cause of these tumors remains a mystery. Unfortunately, they often have a poor prognosis and are often detected at a late stage. The global incidence of gastrointestinal cancers, including those of the stomach, esophagus, colon, liver, and pancreas, is on the rise, leading to a surge in both incidence and mortality. Growth factors and cytokines, which are signaling molecules found in the tumor microenvironment, are thought to be major contributors to the development and metastasis of these cancers. In this review, we explored the role of TNF-α, and its receptors in the development of digestive cancers, including its signaling pathways and functions.
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胃肠道癌症中的 TNF-α 和 TNFR。
肿瘤坏死因子-α(TNF-α)是一种多功能细胞因子,在免疫系统止血、炎症和细胞增殖中发挥作用。然而,它也有阴暗的一面,因为它参与促炎细胞因子和病理过程,如细胞生长和死亡、自身免疫和炎症,导致多种慢性炎症性疾病,包括消化系统癌症。TNF-α 与两种不同的受体(TNFRI 和 TNFRII)结合。配体与这些受体结合后,TNF 受体相关因子(TRAFs)被募集到细胞质受体上,引发 NF-kB 和激活蛋白 1(AP_1)等转录因子的活化。相反,细胞因子与某些家族成员(如 TNF RI 和 Fas 配体(Fas L))结合后,会导致细胞分泌并启动细胞凋亡。胃肠道恶性肿瘤是全球最常见的癌症类型之一。尽管进行了大量研究,但这些肿瘤的确切病因仍然是个谜。不幸的是,这些肿瘤的预后往往很差,而且往往在晚期才被发现。全球胃肠道癌症(包括胃癌、食道癌、结肠癌、肝癌和胰腺癌)的发病率呈上升趋势,导致发病率和死亡率激增。生长因子和细胞因子是肿瘤微环境中的信号分子,被认为是导致这些癌症发展和转移的主要因素。在这篇综述中,我们探讨了 TNF-α 及其受体在消化系统癌症发展中的作用,包括其信号通路和功能。
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来源期刊
CiteScore
5.00
自引率
3.60%
发文量
405
审稿时长
24 days
期刊介绍: Pathology, Research and Practice provides accessible coverage of the most recent developments across the entire field of pathology: Reviews focus on recent progress in pathology, while Comments look at interesting current problems and at hypotheses for future developments in pathology. Original Papers present novel findings on all aspects of general, anatomic and molecular pathology. Rapid Communications inform readers on preliminary findings that may be relevant for further studies and need to be communicated quickly. Teaching Cases look at new aspects or special diagnostic problems of diseases and at case reports relevant for the pathologist''s practice.
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