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Understanding Obesity as a Risk Factor for Uterine Tumors Using Drosophila

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The Drosophila Model in Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1167))

Abstract

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 from Drosophila melanogaster.

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Acknowledgments

We apologize to those colleagues whose work is not cited in this essay due to space limitations or our ignorance and negligence. This work was supported in part by NIH grants R01DK095013 and R01GM129266.

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  1. Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M University Health Science Center, Bryan, TX, USA

    Xiao Li, Mengmeng Liu & Jun-Yuan Ji

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  1. Xiao Li
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  2. Mengmeng Liu
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  3. Jun-Yuan Ji
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Correspondence to Jun-Yuan Ji .

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  1. Department of Biochemistry and Molecular Biology, Tulane Cancer Center, LCRC, Tulane University School of Medicine, New Orleans, LA, USA

    Wu-Min Deng

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Li, X., Liu, M., Ji, JY. (2019). Understanding Obesity as a Risk Factor for Uterine Tumors Using Drosophila. In: Deng, WM. (eds) The Drosophila Model in Cancer. Advances in Experimental Medicine and Biology, vol 1167. Springer, Cham. https://doi.org/10.1007/978-3-030-23629-8_8

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