Mitochondrial Ribosomal Protein S18-2 is Highly Expressed in Endometrial Cancers Along with Free E2F1

Overview

Journal Oncotarget

Specialty Oncology

Date 2016 Mar 10

PMID 26959119

Citations 13

Authors

Miriam Mints

Muhammad Mushtaq

Natalia Iurchenko

Larysa Kovalevska

Maria C Stip

Daria Budnikova

Sonia Andersson

Ludmila Polischuk

Lubov Buchynska

Elena Kashuba

Affiliations

Soon will be listed here.

Abstract

Endometrial cancer (EC) is one of the most frequent causes of cancer death among women in developed countries. Histopathological diagnosis and imaging techniques for EC are limited, thus new prognostic markers are needed to offer patients the best treatment and follow-up.In the present paper we showed that the level of mitochondrial ribosomal protein MRPS18-2 (S18-2) increased in EC compared with the normal endometrium and hyperplasia, based on a study of 42 patient biopsies. Importantly, high expression of free E2F1 in EC correlates well with high S18-2 expression. The EC cell line HEC-1-A, which overexpresses S18-2 constitutively, showed an increased proliferation capacity in vitro and in vivo (in SCID mice). Moreover, pan-keratin, beta-catenin and E-cadherin signals are diminished in these cells, compared to the parental HEC-1-A line, in contrast to vimentin signal that is increased. This may be associated with epithelial-mesenchymal cell transition (EMT).We conclude that high expression of S18-2 and free E2F1, and low pan-keratin, beta-catenin, and E-cadherin signals might be a good set of prognostic markers for EC.

Citing Articles

Mitochondrial ribosomal proteins in metastasis and their potential use as prognostic and therapeutic targets.

Bacon J, Jones J, Liu G, Dickinson J, Raspin K Cancer Metastasis Rev. 2024; 43(4):1119-1135.

PMID: 39354291 PMC: 11554709. DOI: 10.1007/s10555-024-10216-4.

Mechanism of E2F1 in the proliferation, migration, and invasion of endometrial carcinoma cells via the regulation of BMI1 transcription.

Lu Y, Wei Y, Shen X, Tong Y, Lu J, Zhang Y Genes Genomics. 2023; 45(11):1423-1431.

PMID: 37646913 DOI: 10.1007/s13258-023-01416-3.

STK4 protein expression pattern follows different trends in endometrioid and serous endometrial adenocarcinoma upon tumor progression.

Govorov I, Attarha S, Kovalevska L, Andersson E, Kashuba E, Mints M Sci Rep. 2022; 12(1):22154.

PMID: 36550267 PMC: 9780310. DOI: 10.1038/s41598-022-26391-9.

Genetic Polymorphism of E2F1 Influences Susceptibility to Ovarian Cancer in a Chinese Population.

Wu Y, You Z, Xu M Contrast Media Mol Imaging. 2022; 2022:7808726.

PMID: 35833075 PMC: 9252677. DOI: 10.1155/2022/7808726.

Identification of the shared gene signatures and pathways between polycystic ovary syndrome and endometrial cancer: An omics data based combined approach.

Miao C, Chen Y, Fang X, Zhao Y, Wang R, Zhang Q PLoS One. 2022; 17(7):e0271380.

PMID: 35830453 PMC: 9278750. DOI: 10.1371/journal.pone.0271380.

References

Johnson D, DeGregori J . Putting the Oncogenic and Tumor Suppressive Activities of E2F into Context. Curr Mol Med. 2006; 6(7):731-8. DOI: 10.2174/1566524010606070731. View

Prat J . Prognostic parameters of endometrial carcinoma. Hum Pathol. 2004; 35(6):649-62. DOI: 10.1016/j.humpath.2004.02.007. View

Kashuba E, Yurchenko M, Yenamandra S, Snopok B, Isaguliants M, Szekely L . EBV-encoded EBNA-6 binds and targets MRS18-2 to the nucleus, resulting in the disruption of pRb-E2F1 complexes. Proc Natl Acad Sci U S A. 2008; 105(14):5489-94. PMC: 2291094. DOI: 10.1073/pnas.0801053105. View

Kiewisz J, Wasniewski T, Kmiec Z . Participation of WNT and β-Catenin in Physiological and Pathological Endometrial Changes: Association with Angiogenesis. Biomed Res Int. 2015; 2015:854056. PMC: 4558421. DOI: 10.1155/2015/854056. View

Bondow B, Faber M, Wojta K, Walker E, Battle M . E-cadherin is required for intestinal morphogenesis in the mouse. Dev Biol. 2012; 371(1):1-12. PMC: 3455111. DOI: 10.1016/j.ydbio.2012.06.005. View

Samarnthai N, Hall K, Yeh I . Molecular profiling of endometrial malignancies. Obstet Gynecol Int. 2010; 2010:162363. PMC: 2846683. DOI: 10.1155/2010/162363. View

Mannelqvist M, Stefansson I, Salvesen H, Akslen L . Importance of tumour cell invasion in blood and lymphatic vasculature among patients with endometrial carcinoma. Histopathology. 2009; 54(2):174-83. DOI: 10.1111/j.1365-2559.2008.03201.x. View

Yin Y, Shen W . PTEN: a new guardian of the genome. Oncogene. 2008; 27(41):5443-53. DOI: 10.1038/onc.2008.241. View

Zaragoza K, Begay V, Schuetz A, Heinemann U, Leutz A . Repression of transcriptional activity of C/EBPalpha by E2F-dimerization partner complexes. Mol Cell Biol. 2010; 30(9):2293-304. PMC: 2863587. DOI: 10.1128/MCB.01619-09. View

10.

Witkiewicz A, Knudsen K, Dicker A, Knudsen E . The meaning of p16(ink4a) expression in tumors: functional significance, clinical associations and future developments. Cell Cycle. 2011; 10(15):2497-503. PMC: 3685613. DOI: 10.4161/cc.10.15.16776. View

11.

Shevchuk Z, Yurchenko M, Darekar S, Holodnuka-Kholodnyuk I, Kashuba V, Kashuba E . Overexpression of MRPS18-2 in Cancer Cell Lines Results in Appearance of Multinucleated Cells. Acta Naturae. 2013; 5(1):85-9. PMC: 3612828. View

12.

Mhawech-Fauceglia P, Wang D, Kesterson J, Clark K, Monhollen L, Odunsi K . Microarray analysis reveals distinct gene expression profiles among different tumor histology, stage and disease outcomes in endometrial adenocarcinoma. PLoS One. 2010; 5(11):e15415. PMC: 2975707. DOI: 10.1371/journal.pone.0015415.s001. View

13.

Kashuba E, Yenamandra S, Darekar S, Yurchenko M, Kashuba V, Klein G . MRPS18-2 protein immortalizes primary rat embryonic fibroblasts and endows them with stem cell-like properties. Proc Natl Acad Sci U S A. 2009; 106(47):19866-71. PMC: 2785258. DOI: 10.1073/pnas.0911545106. View

14.

Matias-Guiu X, Prat J . Molecular pathology of endometrial carcinoma. Histopathology. 2012; 62(1):111-23. DOI: 10.1111/his.12053. View

15.

Werner H, Salvesen H . Current status of molecular biomarkers in endometrial cancer. Curr Oncol Rep. 2014; 16(9):403. DOI: 10.1007/s11912-014-0403-3. View

16.

Buchynska L, Nesina I, Kashuba E . Different trends of p53, MDM2 and p14 ARF expression patterns in endometrial adenocarcinomas versus hyperplasia. Exp Oncol. 2008; 29(4):287-94. View

17.

Salvesen H, Carter S, Mannelqvist M, Dutt A, Getz G, Stefansson I . Integrated genomic profiling of endometrial carcinoma associates aggressive tumors with indicators of PI3 kinase activation. Proc Natl Acad Sci U S A. 2009; 106(12):4834-9. PMC: 2660768. DOI: 10.1073/pnas.0806514106. View

18.

Koul A, Willen R, Bendahl P, Nilbert M, Borg A . Distinct sets of gene alterations in endometrial carcinoma implicate alternate modes of tumorigenesis. Cancer. 2002; 94(9):2369-79. DOI: 10.1002/cncr.10498. View

19.

Snopok B, Yurchenko M, Szekely L, Klein G, Kashuba E . SPR-based immunocapture approach to creating an interfacial sensing architecture: Mapping of the MRS18-2 binding site on retinoblastoma protein. Anal Bioanal Chem. 2006; 386(7-8):2063-73. DOI: 10.1007/s00216-006-0867-6. View

20.

Helin K, Harlow E, Fattaey A . Inhibition of E2F-1 transactivation by direct binding of the retinoblastoma protein. Mol Cell Biol. 1993; 13(10):6501-8. PMC: 364709. DOI: 10.1128/mcb.13.10.6501-6508.1993. View