Fumarate hydratase functions as a tumor suppressor in endometrial cancer by inactivating EGFR signaling

  • Authors:
    • Yen-Yun Wang
    • Anupama Vadhan
    • Ching-Hu Wu
    • Cheng-Yang Hsu
    • Yu-Chieh Chen
    • Yuk-Kwan Chen
    • Pang-Yu Chen
    • Hieu D.h. Nguyen
    • Yu-Chiuan Chang
    • Shyng-Shiou F. Yuan
  • View Affiliations

  • Published online on: August 23, 2023     https://doi.org/10.3892/or.2023.8620
  • Article Number: 183
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Abstract

Fumarase hydratase (FH) is an enzyme that catalyzes the reversible hydration and dehydration of fumarate to malate in the tricarboxylic acid cycle. The present study addressed the role of FH in endometrial cancer and clinically observed that the expression of FH was significantly lower in endometrial cancer tissues compared with normal endometrial tissues and, furthermore, that the decreased FH expression in endometrial cancer tissues was significantly associated with increased tumor size and lymph node metastasis. Further analysis in in vitro study showed that cell proliferation, migration and invasion abilities were increased when the expression of FH in the endometrial cancer cells was knocked down, but, by contrast, overexpression of FH in endometrial cancer cells decreased cell proliferative, migratory and invasive abilities. Mechanistic studies showed that the expression of vimentin and twist, being two well-studied mesenchymal markers in endometrial cancer cells, were upregulated in fumarate hydratase-knockdowned cells. In addition, phosphokinase array analysis demonstrated that the expression of phospho-EGFR (Y1086), which promotes carcinogenesis in cancers, was increased in endometrial cancer cells when FH was knocked down. In conclusion, the present study suggested that FH is a tumor suppressor and inhibits endometrial cancer cell proliferation and metastasis by inactivation of EGFR. Further studies are required to clarify its role as a prognostic biomarker and therapeutic target for endometrial cancer.
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October-2023
Volume 50 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Wang Y, Vadhan A, Wu C, Hsu C, Chen Y, Chen Y, Chen P, Nguyen HD, Chang Y, Yuan SF, Yuan SF, et al: Fumarate hydratase functions as a tumor suppressor in endometrial cancer by inactivating EGFR signaling. Oncol Rep 50: 183, 2023.
APA
Wang, Y., Vadhan, A., Wu, C., Hsu, C., Chen, Y., Chen, Y. ... Yuan, S.F. (2023). Fumarate hydratase functions as a tumor suppressor in endometrial cancer by inactivating EGFR signaling. Oncology Reports, 50, 183. https://doi.org/10.3892/or.2023.8620
MLA
Wang, Y., Vadhan, A., Wu, C., Hsu, C., Chen, Y., Chen, Y., Chen, P., Nguyen, H. D., Chang, Y., Yuan, S. F."Fumarate hydratase functions as a tumor suppressor in endometrial cancer by inactivating EGFR signaling". Oncology Reports 50.4 (2023): 183.
Chicago
Wang, Y., Vadhan, A., Wu, C., Hsu, C., Chen, Y., Chen, Y., Chen, P., Nguyen, H. D., Chang, Y., Yuan, S. F."Fumarate hydratase functions as a tumor suppressor in endometrial cancer by inactivating EGFR signaling". Oncology Reports 50, no. 4 (2023): 183. https://doi.org/10.3892/or.2023.8620