Understanding Obesity as a Risk Factor for Uterine Tumors Using Drosophila.
Understanding Obesity as a Risk Factor for Uterine Tumors Using Drosophila.
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使用果蝇了解肥胖作为子宫肿瘤的危险因素。
DOI：
10.1007/978-3-030-23629-8_8
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发表时间：
2019
影响因子：
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通讯作者：
Ji,Jun-Yuan
中科院分区：
文献类型：
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作者：
Li,Xiao;Liu,Mengmeng;Ji,Jun-Yuan
多项大规模流行病学研究已确定肥胖是多种人类癌症的重要危险因素，特别是子宫癌、胆囊癌、肾癌、肝癌、结肠癌和卵巢癌，但肥胖如何增加癌症风险尚存在很大不确定性。鉴于肥胖一直被认为是女性生殖系统最常见恶性肿瘤子宫肿瘤的主要危险因素，我们以子宫肿瘤为病理背景，调查了相关文献，并提出了一个新的假设：细胞周期蛋白依赖性激酶8（CDK8）模块的慢性下调，该模块由CDK8（或其旁系同源物CDK19）、细胞周期蛋白C、MED12（或MED12L）和MED13（或MED13L），肥胖女性中胰岛素或胰岛素样生长因子信号传导升高可能会增加由 CDK8 模块调节的转录因子活性失调的机会，从而增加子宫肿瘤的风险。尽管我们关注子宫内膜癌和子宫肌瘤（或肌瘤）这两种主要的子宫肿瘤形式，但我们的模型可能会为肥胖如何增加其他类型癌症和疾病的风险提供更多见解。为了说明模式生物在研究人类疾病方面的力量，在这里我们更加强调从黑腹果蝇中获得的研究结果。
Multiple large-scale epidemiological studies have identified obesity as an important risk factor for a variety of human cancers, particularly cancers of the uterus, gallbladder, kidney, liver, colon, and ovary, but there is much uncertainty regarding how obesity increases the cancer risks. Given that obesity has been consistently identified as a major risk factor for uterine tumors, the most common malignancies of the female reproductive system, we use uterine tumors as a pathological context to survey the relevant literature and propose a novel hypothesis: chronic downregulation of the cyclin-dependent kinase 8 (CDK8) module, composed of CDK8 (or its paralog CDK19), Cyclin C, MED12 (or MED12L), and MED13 (or MED13L), by elevated insulin or insulin-like growth factor signaling in obese women may increase the chances to dysregulate the activities of transcription factors regulated by the CDK8 module, thereby increasing the risk of uterine tumors. Although we focus on endometrial cancer and uterine leiomyomas (or fibroids), two major forms of uterine tumors, our model may offer additional insights into how obesity increases the risk of other types of cancers and diseases. To illustrate the power of model organisms for studying human diseases, here we place more emphasis on the findings obtained fromDrosophila melanogaster.