Active Estrogen–Succinate Metabolism Promotes Heme Accumulation and Increases the Proliferative and Invasive Potential of Endometrial Cancer Cells

The mechanisms of estrogen–succinate–heme metabolism in uterine endometrial cancer. (1) Estrogen can inhibit SDHB expression through the PPARγ-SP1-UBC pathway, promoting the accumulation of succinate in UEC. The abnormal accumulation of succinate promotes heme synthesis and upregulates ER levels, especially those of ERβ. (2) Estrogen activates the expression of NCOA1 mainly through ERβ, increasing the synthesis of ALAS1. (3) Glycine can be transported into the mitochondria under the mediation of SLC25A38 and eventually participate in heme biosynthesis. Estrogen and succinate synergistically increase the accumulation of free heme, which promotes the proliferation and invasiveness of cells, accelerating the progression of UEC. SDHB: succinate dehydrogenase B; PPARγ: peroxisome proliferator-activated receptor γ; SP1: specificity protein 1; UBC: ubiquitin C; UEC: uterine endometrial cancer; ER: estrogen receptor; NCOA1: nuclear receptor coactivator 1; ALAS1: aminolevulinate delta synthase 1; SLC25A38: solute carrier family 25 A38.

Publication

Active Estrogen–Succinate Metabolism Promotes Heme Accumulation and Increases the Proliferative and Invasive Potential of Endometrial Cancer Cells. (2023) Jia-Jing Lu, et al. Biomolecules. 2023 Jul;13(7):1097. Figure: F9. Homo sapiens

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