American Association for Cancer Research
00085472can140208-sup-can-14-0208tab1.pdf (138.45 kB)

Supplementary Table 1 from Separating Tumorigenicity from Bile Acid Regulatory Activity for Endocrine Hormone FGF19

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journal contribution
posted on 2023-03-30, 22:46 authored by Mei Zhou, Xueyan Wang, Van Phung, Darrin A. Lindhout, Kalyani Mondal, Jer-Yuan Hsu, Hong Yang, Mark Humphrey, Xunshan Ding, Taruna Arora, R. Marc Learned, Alex M. DePaoli, Hui Tian, Lei Ling

PDF file - 142KB, Supplementary Table S1. Serum Parameters of db/db Mice After Continuous Exposure to FGF19 or M70 for 24 Weeks.



Hepatocellular carcinoma (HCC), one of the leading causes of cancer-related death, develops from premalignant lesions in chronically damaged livers. Although it is well established that FGF19 acts through the receptor complex FGFR4-β-Klotho (KLB) to regulate bile acid metabolism, FGF19 is also implicated in the development of HCC. In humans, FGF19 is amplified in HCC and its expression is induced in the liver under cholestatic and cirrhotic conditions. In mice, ectopic overexpression of FGF19 drives HCC development in a process that requires FGFR4. In this study, we describe an engineered FGF19 (M70) that fully retains bile acid regulatory activity but does not promote HCC formation, demonstrating that regulating bile acid metabolism is distinct and separable from tumor-promoting activity. Mechanistically, we show that FGF19 stimulates tumor progression by activating the STAT3 pathway, an activity eliminated by M70. Furthermore, M70 inhibits FGF19-dependent tumor growth in a rodent model. Our results suggest that selectively targeting the FGF19–FGFR4 pathway may offer a tractable approach to improve the treatment of chronic liver disease and cancer. Cancer Res; 74(12); 3306–16. ©2014 AACR.

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