PDK1在肿瘤发生及组织器官发育中的功能
Roles of PDK1 in tumorigenesis and organ development
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摘要:
环境因素如大气和水污染、重金属暴露、病毒感染等常通过影响多种细胞信号转导通路导致基因突变的积累进而引发肿瘤，甚至导致严重的发育缺陷。细胞内多种信号通路对环境因素都极为敏感，其中3-磷脂酰肌醇依赖的蛋白激酶-1（PDK1）介导的多个信号通路参与调控细胞的增殖、分化、迁移和凋亡，同时也调节多种组织器官包括中枢神经系统的发育。PDK1相关通路的异常可引发多种发育缺陷如神经管闭合不全、小头症、智力障碍以及肺癌、结肠癌、乳腺癌、卵巢癌、前列腺癌等肿瘤的发生。PDK1与肿瘤组织形成、浸染、转移以及微环境之间的关系是目前肿瘤领域研究热点之一，作为多种肿瘤诊疗的一个潜在靶点，PDK1受到了广泛关注。因此深入了解PDK1相关通路的调控机制以及环境因素对这些相关信号转导中的影响可为发育畸变、肿瘤发生等疾病的预防和干预提供新的视角，并为早期诊疗提供线索和理论指导。
Abstract: Environmental factors, such as air or water pollution, heavy metal exposure, and virus infection, often cause accumulations in gene mutations, subsequent tumors, and even developmental defects through intracellular signaling transduction pathways. Multiple intracellular signaling pathways are sensitive to environmental factors, and among them 3-phosphoinositide dependent protein kinase-1 (PDK1) is a key element involved in several signaling transduction pathways mediating cell proliferation, differentiation, metastasis, and apoptosis, as well as tissue and organ development such as central nerve system. It has been reported that abnormalities in PDK1 signaling pathways lead to developmental defects such as dysraphism, microcephaly, mental retardation, and cancers in many organs including lung, colon, breast, ovarian, and prostate. PDK1 in associations with tumor formation, invasion, metastasis, and microenvironment are hot spots in cancer research nowadays, and as a potential therapeutic target, PDK1 has received wide attentions. Therefore, to further understand the regulation mechanisms related to PDK1 signaling pathways and the effects of environmental factors can provide new perspectives to prevent and intervene developmental mutations and tumorigenesis, as well as provide clues and theoretical guidance for early diagnosis and treatment.
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