Loss of Sun2 Promotes the Progression of Prostate Cancer by Regulating Fatty Acid Oxidation

Overview

Journal Oncotarget

Specialty Oncology

Date 2017 Nov 23

PMID 29163775

Citations 12

Authors

Cheng Yajun

Ye Chen

Li Xiaosa

Wang Xiao

Chen Jia

Wang Zhong

Xu Bin

Affiliations

Soon will be listed here.

Abstract

The role of Sun2 has been described by previous studies in various types of cancers, including breast cancer and lung cancer. However, its role and potential molecular mechanism in the progression of prostate cancer have not been fully elucidated. In the present study, we found that Sun2 expression was reduced in prostate cancer tissues compared with paired normal tissues, and that low expression of Sun2 was significantly correlated with Higher Gleason scores, postoperative T stage (pT), Lymph nodal invasion and Clinical pathological stages. In addition, reduced Sun2 Expression predicts poor survival of prostate cancer patients and could serve as an independent predictor of prostate cancer patients overall survival (OS).Furthermore, Sun2 overexpression inhibits the prostate cancer cells growth, and Sun2 knockdown promotes the prostate cancer cells growth both and . Mechanical silencing of , Sun2 promoted fatty acid oxidation (FAO) in prostate cancer, prostate cancer cells growth promoted by Sun2 silencing could be reversed by the FAO inhibitor Etomoxir. Additionally, we also showed that serum amyloid A1 (SAA1) play a vital role in FAO, ATP and cell growth promoted by Sun2 loss in prostate cancer. These results suggest that Loss of Sun2 promoted the prostate cancer progression by regulating FAO.

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References

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M . Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2014; 136(5):E359-86. DOI: 10.1002/ijc.29210. View

Warburg O . On the origin of cancer cells. Science. 1956; 123(3191):309-14. DOI: 10.1126/science.123.3191.309. View

Shimi T, Butin-Israeli V, Goldman R . The functions of the nuclear envelope in mediating the molecular crosstalk between the nucleus and the cytoplasm. Curr Opin Cell Biol. 2011; 24(1):71-8. PMC: 3339630. DOI: 10.1016/j.ceb.2011.11.007. View

Kitajima K, Murphy R, Nathan M, Sugimura K . Update on positron emission tomography for imaging of prostate cancer. Int J Urol. 2013; 21(1):12-23. DOI: 10.1111/iju.12250. View

Cuzick J, Thorat M, Andriole G, Brawley O, Brown P, Culig Z . Prevention and early detection of prostate cancer. Lancet Oncol. 2014; 15(11):e484-92. PMC: 4203149. DOI: 10.1016/S1470-2045(14)70211-6. View

Lloyd M, Yevglevskis M, Lee G, Wood P, Threadgill M, Woodman T . α-Methylacyl-CoA racemase (AMACR): metabolic enzyme, drug metabolizer and cancer marker P504S. Prog Lipid Res. 2013; 52(2):220-30. DOI: 10.1016/j.plipres.2013.01.001. View

Donahue D, Amraoui S, Di Nunzio F, Kieffer C, Porrot F, Opp S . SUN2 Overexpression Deforms Nuclear Shape and Inhibits HIV. J Virol. 2016; 90(8):4199-4214. PMC: 4810566. DOI: 10.1128/JVI.03202-15. View

Maraldi N, Lattanzi G, Cenni V, Bavelloni A, Marmiroli S, Manzoli F . Laminopathies and A-type lamin-associated signalling pathways. Adv Enzyme Regul. 2009; 50(1):248-61. DOI: 10.1016/j.advenzreg.2009.10.019. View

Wei Z, Liang C, Feng D, Cheng Y, Wang W, Yang D . Low tristetraprolin expression promotes cell proliferation and predicts poor patients outcome in pancreatic cancer. Oncotarget. 2016; 7(14):17737-50. PMC: 4951246. DOI: 10.18632/oncotarget.7397. View

10.

Isermann P, Lammerding J . Nuclear mechanics and mechanotransduction in health and disease. Curr Biol. 2013; 23(24):R1113-21. PMC: 3883624. DOI: 10.1016/j.cub.2013.11.009. View

11.

Chen W, Zheng R, Baade P, Zhang S, Zeng H, Bray F . Cancer statistics in China, 2015. CA Cancer J Clin. 2016; 66(2):115-32. DOI: 10.3322/caac.21338. View

12.

Chen C, Wang P, Liu B, Hsu H, Mersmann H, Ding S . Serum amyloid A protein regulates the expression of porcine genes related to lipid metabolism. J Nutr. 2008; 138(4):674-9. DOI: 10.1093/jn/138.4.674. View

13.

Schlaepfer I, Rider L, Rodrigues L, Gijon M, Pac C, Romero L . Lipid catabolism via CPT1 as a therapeutic target for prostate cancer. Mol Cancer Ther. 2014; 13(10):2361-71. PMC: 4185227. DOI: 10.1158/1535-7163.MCT-14-0183. View

14.

Xu S, Yi X, Zhou W, Cheng W, Ge J, Zhang Z . Downregulation of miR-129 in peripheral blood mononuclear cells is a diagnostic and prognostic biomarker in prostate cancer. Int J Clin Exp Pathol. 2016; 8(11):14335-44. PMC: 4713535. View

15.

Matsumoto A, Hieda M, Yokoyama Y, Nishioka Y, Yoshidome K, Tsujimoto M . Global loss of a nuclear lamina component, lamin A/C, and LINC complex components SUN1, SUN2, and nesprin-2 in breast cancer. Cancer Med. 2015; 4(10):1547-57. PMC: 4618625. DOI: 10.1002/cam4.495. View

16.

Ferlay J, Shin H, Bray F, Forman D, Mathers C, Parkin D . Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2011; 127(12):2893-917. DOI: 10.1002/ijc.25516. View

17.

Lv X, Liu L, Cheng C, Yu B, Xiong L, Hu K . SUN2 exerts tumor suppressor functions by suppressing the Warburg effect in lung cancer. Sci Rep. 2015; 5:17940. PMC: 4674702. DOI: 10.1038/srep17940. View

18.

Vander Heiden M, Cantley L, Thompson C . Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009; 324(5930):1029-33. PMC: 2849637. DOI: 10.1126/science.1160809. View

19.

Hsieh T, Chien C, Lee Y, Lin C, Hsieh J, Chao M . Downregulation of SUN2, a novel tumor suppressor, mediates miR-221/222-induced malignancy in central nervous system embryonal tumors. Carcinogenesis. 2014; 35(10):2164-74. DOI: 10.1093/carcin/bgu105. View

20.

Zhu X, Albertsen P, Andriole G, Roobol M, Schroder F, Vickers A . Risk-based prostate cancer screening. Eur Urol. 2011; 61(4):652-61. PMC: 4716732. DOI: 10.1016/j.eururo.2011.11.029. View