Knockdown of FAM83D inhibits endometrial cancer cell viability and induces autophagy via the PI3K/AKT/mTOR axis
1Department of Medical, Wuhan City College, 430083 Wuhan, Hubei, China
2Department of Obstetrics and Gynecology, Yulin First Hospital, 718000 Yulin, Shaanxi, China
DOI: 10.22514/ejgo.2022.033 Vol.43,Issue 4,August 2022 pp.64-71
Submitted: 25 May 2022 Accepted: 04 July 2022
Published: 15 August 2022
It is important to search new diagnostic and prognostic markers of endometrial cancer (EC) and uncover the possible mechanisms. Family with sequence similarity 83 member D (FAM83D) is proved to have carcinogenic properties and act as a new oncogene. FAM83D is overexpressed in endometrial cancer, but the role of FAM83D in EC is still unclear. Here the role of FAM83D was investigated in EC progression. FAM83D depletion inhibited the proliferation of EC cells. The knockdown of FAM83D induced EC cell cycle arrest. Moreover, its depletion stimulated the apoptosis and autophagy of EC cells. We further found FAM83D depletion inhibited progression of EC via targeting phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) axis. We therefore thought FAM83D could serve as a EC target.
FAM83D; Endometrial cancer (EC); Apoptosis; Autophagy; PI3K/AKT/mTOR pathway
Zhou Cai,Yan Mei,Xiaoye Jiang,Ruiqin Li. Knockdown of FAM83D inhibits endometrial cancer cell viability and induces autophagy via the PI3K/AKT/mTOR axis. European Journal of Gynaecological Oncology. 2022. 43(4);64-71.
 Pitakkarnkul S, Chanpanitkitchot S, Tangjitgamol S. Management of inoperable endometrial cancer. To be published in Obstetrics & Gynecology Science. 2022. [Preprint].
 An HJ, Song DH, Kim YM, Jo HC, Baek JC, Park JE. Significance of HER2 and VEGFR2 in early-stage endometrial cancer. In Vivo. 2022; 36: 723–730.
 Králíčková M, Vetvicka V, Laganà AS. Endometrial cancer—is our knowledge changing? Translational Cancer Research. 2020; 9: 7734–7745.
 Redondo A, Gallego A, Mendiola M. Dostarlimab for the treatment of advanced endometrial cancer. Expert Review of Clinical Pharmacology. 2022; 15: 1–9.
 Camilloni A, Nati G, Maggiolini P, Romanelli A, Carbone G, Giannarelli D, et al. Chronic non-cancer pain in primary care: an Italian cross-sectional study. Signa Vitae. 2021; 17: 54–62.
 Meng T, Tong Z, Yang M, Zhang Y, Liu Y, Wang Z, et al. Immune implication of FAM83D gene in hepatocellular carcinoma. Bioengineered. 2021; 12: 3578–3592.
 Zhu H, Diao S, Lim V, Hu L, Hu J. FAM83D inhibits autophagy and promotes proliferation and invasion of ovarian cancer cells via PI3K/AKT/mTOR pathway. Acta Biochimica Et Biophysica Sinica. 2019; 51: 509–516.
 Yu C, Cheng Z, Cui S, Mao X, Li B, Fu Y, et al. CircFOXM1 promotes proliferation of non-small cell lung carcinoma cells by acting as a ceRNA to upregulate FAM83D. Journal of Experimental & Clinical Cancer Research. 2020; 39: 55.
 Yang XX, Ma M, Sang MX, Zhang XY, Zou NY, Zhu SC. Knockdown of FAM83D enhances radiosensitivity in coordination with irradiation by inhibiting EMT via the Akt/GSK-3β/Snail signaling pathway in human esophageal cancer cells. OncoTargets and Therapy. 2020; 13: 4665–4678.
 Huang M, Ma X, Shi H, Hu L, Fan Z, Pang L, et al. FAM83D, a microtubule-associated protein, promotes tumor growth and progression of human gastric cancer. Oncotarget. 2017; 8: 74479–74493.
 Zhang Q, Yu S, Lok SIS, Wong AST, Jiao Y, Lee LTO. FAM83D promotes ovarian cancer progression and its potential application in diagnosis of invasive ovarian cancer. Journal of Cellular and Molecular Medicine. 2019; 23: 4569–4581.
 Barra F, Evangelisti G, Ferro Desideri L, Di Domenico S, Ferraioli D, Vellone VG, et al. Investigational PI3K/AKT/mTOR inhibitors in development for endometrial cancer. Expert Opinion on Investigational Drugs. 2019; 28: 131–142.
 Hsin IL, Shen HP, Chang HY, Ko JL, Wang PH. Suppression of PI3K/Akt/mTOR/c-Myc/mtp53 positive feedback loop induces cell cycle arrest by dual PI3K/mTOR Inhibitor PQR309 in endometrial cancer cell lines. Cells. 2021; 10: 2916.
 Qu J, Sun Y, Yang L, Niu X, Li L. Fucoxanthin prevents cell growth and induces apoptosis in endometrial cancer HEC-1a cells by the inhibition of the PI3K/Akt/mTOR pathway. Journal of Biochemical and Molecular Toxicology. 2022; 36: e23027.
 Uyar DS, Huang Y, Chesnik MA, Doan NB, Mirza SP. Comprehensive serum proteomic analysis in early endometrial cancer. Journal of Proteomics. 2021; 234: 104099.
 Mutch DG. Targeted therapy in endometrial cancer: making progress. Cancer. 2016; 122: 3428–3429.
 Wang J, Quan Y, Lv J, Gong S, Ren P. Inhibition of FAM83D displays antitumor effects in glioblastoma via down-regulation of the AKT/Wnt/β-catenin pathway. Environmental Toxicology. 2022; 37: 1343–1356.
 Cooper LM, Hanson A, Kavanagh JA, Waddell DS. Fam83d modulates MAP kinase and AKT signaling and is induced during neurogenic skeletal muscle atrophy. Cellular Signalling. 2020; 70: 109576.
 Yin C, Lin X, Wang Y, Liu X, Xiao Y, Liu J, et al. FAM83D promotes
epithelial-mesenchymal transition, invasion and cisplatin resistance through regulating the AKT/mTOR pathway in non-small-cell lung cancer. Cellular Oncology. 2020; 43: 395–407.
 Jia M, Qiu H, Lin L, Zhang S, Li D, Jin D. Inhibition of PI3K/AKT/mTOR signalling pathway activates autophagy and suppresses peritoneal fibrosis in the process of peritoneal dialysis. Frontiers in Physiology. 2022; 13: 778479.
 Barzegar Behrooz A, Talaie Z, Jusheghani F, Los MJ, Klonisch T, Ghavami S. Wnt and PI3K/Akt/mTOR survival pathways as therapeutic targets in glioblastoma. International Journal of Molecular Sciences. 2022; 23: 1353.
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