The incidence of endometrial cancer(EC)increases annually and tends to occur in younger women.A particularly important relationship exists between EC and metabolic disorders.As one of the most important components of lipid metabolism,phospholipids play an indispensable role in metabolic balance.LPCAT1 is a key enzyme regulating phospholipid metabolism.In this study,we perform further investigations to seek mechanistic insight of LPCAT1 in EC.Our results demonstrate that silencing of LPCAT1 inhibits the growth of endometrial cancer,while over-expression of LPCAT1 results in enhanced stemness and metastasis in endometrial cancer cell lines.Meanwhile,the contents of various phospholipids including phosphatidylethanolamine(PE),phosphatidylcholine(PC),and trigly-ceride(TG)change significantly after overexpression of LPCAT1.In addition,through RNA-sequencing and western blot analysis,we observe that the TGF-β/Smad2/3 signaling pathway is of great importance in the tumor-promoting function of LPCAT1.LPCAT1 promotes the expressions of stem cell-related transcription factors and epithelial-mesenchymal transition(EMT)related proteins through the TGF-β/Smad2/3 signaling pathway.Moreover,we find that TSI-01,which can inhibit the activity of LPCAT1,is able to restrain the proliferation of EC cell lines and promote cell apoptosis.Collectively,we demonstrate that LPCAT1 enhances the stemness and metastasis of EC by activating the TGF-β/Smad2/3 signaling pathway and that TSI-01 may have potential use for the treatment of EC.

Tianyi Zhao;Rui Sun;Xiaohong Ma;Lina Wei;Yixin Hou;Kun Song;Jie Jiang

Department of Gynecology and Obstetrics,Qilu Hospital,Cheeloo College of Medicine,Shandong University,Jinan 250012,China

生物化学与生物物理学报（英文版）

[1]Tianyi Zhao;Rui Sun;Xiaohong Ma;Lina Wei;Yixin Hou;Kun Song;Jie Jiang-.Overexpression of LPCAT1 enhances endometrial cancer stemness and metastasis by changing lipid components and activating TGF-β/Smad2/3 signaling pathway)[J].生物化学与生物物理学报（英文版）,2022(07):904-916

LPCAT1,trigly,ceride

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