Impact of FOXL2 mutations on signaling in ovarian granulosa cell tumors

The International Journal of Biochemistry & Cell Biology
Dilys T H LeungSimon Chu

Abstract

Granulosa cell tumors (GCT) are unique sex-cord stromal tumors which account for ∼ 8% of all ovarian malignancies. They exhibit morphological, biochemical and hormonal features similar to proliferating granulosa cells of the preovulatory follicle, including estrogen and inhibin synthesis. A somatic missense mutation in the forkhead box L2 (FOXL2) gene (C134W) is unique to adult GCT, and absent in other ovarian cancers. FOXL2 is a transcription factor that plays a critical role in ovarian function, in particular, proliferation and differentiation of granulosa cells. The molecular mechanisms underlying the pathogenicity of the mutant FOXL2 remain unresolved. Here we review the molecular alterations known to be associated with mutant FOXL2 and the potential signaling implications. Several studies suggest that dysregulated FOXL2 function may alter cell cycle progression and apoptosis. Further insights into the molecular mechanism of GCT pathophysiology may identify therapeutic targets for the treatment of these tumors.

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Citations

Nov 5, 2016·Clinical Genetics·P J FullerS Chu
Feb 23, 2018·Endocrinology·Martina BelliShunichi Shimasaki
Feb 17, 2018·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Jessica A PilsworthDavid G Huntsman
Feb 8, 2018·Journal of Ovarian Research·Jiaheng LiChunping Zhang
Jun 6, 2019·Toxicological Sciences : an Official Journal of the Society of Toxicology·Frank J SimutisMichael J Graziano
Nov 9, 2019·Journal of the Endocrine Society·Martina BelliShunichi Shimasaki
Aug 15, 2019·Abdominal Radiology·Sherif ElsherifPriya Bhosale
Jun 26, 2020·Cancers·Simon P LangdonCharlie Gourley
Jul 13, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Luisa Bonilla, Amit M Oza
Mar 1, 2021·Journal of Translational Medicine·Christian SecchiShunichi Shimasaki
May 25, 2021·Acta Obstetricia Et Gynecologica Scandinavica·Junting LiBeihua Kong
Oct 24, 2021·The Journal of Pathology·Peter J FullerSimon Chu

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