Nuclear Endonuclease G Controls Cell Proliferation in Ovarian Cancer

Overview

Journal FEBS Open Bio

Specialty Biology

Date 2023 Feb 3

PMID 36734593

Authors

Ye Na Choi

Tae Woong Seo

Yui Taek Lee

Dar Heum Jeong

Soon Ji Yoo

Affiliations

Soon will be listed here.

Abstract

Ovarian cancer is characterized by a high degree of genetic heterogeneity. Platinum-based chemotherapy and some gene-targeted therapies have shown limited treatment efficacy due to toxicity and recurrence, and thus, it is essential to identify additional therapeutic targets based on an understanding of the pathological mechanism. Here, we report that endonuclease G, which exhibits altered expression in ovarian cancer, does not function as a cell death effector that digests chromosomal DNA in ovarian cancer. Endonuclease G is modulated by intracellular reactive oxygen species dynamics and plays a role in cell proliferation in ovarian cancer, suggesting that targeting endonuclease G alone or in combination with other antitumor agents may have the potential for development into a treatment for endonuclease G-overexpressing cancers, including ovarian cancer.

Citing Articles

Mitochondrial Factors in the Cell Nucleus.

Gonzalez-Arzola K, Diaz-Quintana A Int J Mol Sci. 2023; 24(17).

PMID: 37686461 PMC: 10563088. DOI: 10.3390/ijms241713656.

A signature based on anoikis-related genes for the evaluation of prognosis, immunoinfiltration, mutation, and therapeutic response in ovarian cancer.

Duan Y, Xu X Front Endocrinol (Lausanne). 2023; 14:1193622.

PMID: 37383389 PMC: 10295154. DOI: 10.3389/fendo.2023.1193622.

References

Steigemann P, Wurzenberger C, Schmitz M, Held M, Guizetti J, Maar S . Aurora B-mediated abscission checkpoint protects against tetraploidization. Cell. 2009; 136(3):473-84. DOI: 10.1016/j.cell.2008.12.020. View

Yoo N, Jeong E, Kim M, Ahn C, Kim S, Lee S . Increased expression of endonuclease G in gastric and colorectal carcinomas. Tumori. 2008; 94(3):351-5. DOI: 10.1177/030089160809400311. View

Matulonis U, Sood A, Fallowfield L, Howitt B, Sehouli J, Karlan B . Ovarian cancer. Nat Rev Dis Primers. 2016; 2:16061. PMC: 7290868. DOI: 10.1038/nrdp.2016.61. View

Huttlin E, Ting L, Bruckner R, Gebreab F, Gygi M, Szpyt J . The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell. 2015; 162(2):425-440. PMC: 4617211. DOI: 10.1016/j.cell.2015.06.043. View

Lee J, Seo T, Yi J, Shin K, Yoo S . CHIP has a protective role against oxidative stress-induced cell death through specific regulation of endonuclease G. Cell Death Dis. 2013; 4:e666. PMC: 3698548. DOI: 10.1038/cddis.2013.181. View

Gerschenson M, Houmiel K, Low R . Endonuclease G from mammalian nuclei is identical to the major endonuclease of mitochondria. Nucleic Acids Res. 1995; 23(1):88-97. PMC: 306634. DOI: 10.1093/nar/23.1.88. View

Wang X, Tryndyak V, Apostolov E, Yin X, Shah S, Pogribny I . Sensitivity of human prostate cancer cells to chemotherapeutic drugs depends on EndoG expression regulated by promoter methylation. Cancer Lett. 2008; 270(1):132-43. PMC: 5091799. DOI: 10.1016/j.canlet.2008.04.053. View

Jang D, Penthala N, Apostolov E, Wang X, Crooks P, Basnakian A . Novel cytoprotective inhibitors for apoptotic endonuclease G. DNA Cell Biol. 2014; 34(2):92-100. PMC: 4308826. DOI: 10.1089/dna.2014.2530. View

Yu F, Sugawara T, Nishi T, Liu J, Chan P . Overexpression of SOD1 in transgenic rats attenuates nuclear translocation of endonuclease G and apoptosis after spinal cord injury. J Neurotrauma. 2006; 23(5):595-603. DOI: 10.1089/neu.2006.23.595. View

10.

Lin J, Nakagawa A, Skeen-Gaar R, Yang W, Zhao P, Zhang Z . Oxidative Stress Impairs Cell Death by Repressing the Nuclease Activity of Mitochondrial Endonuclease G. Cell Rep. 2016; 16(2):279-287. PMC: 5483177. DOI: 10.1016/j.celrep.2016.05.090. View

11.

Wiehe R, Gole B, Chatre L, Walther P, Calzia E, Ricchetti M . Endonuclease G promotes mitochondrial genome cleavage and replication. Oncotarget. 2018; 9(26):18309-18326. PMC: 5915074. DOI: 10.18632/oncotarget.24822. View

12.

Basnakian A, Apostolov E, Yin X, Abiri S, Stewart A, Singh A . Endonuclease G promotes cell death of non-invasive human breast cancer cells. Exp Cell Res. 2006; 312(20):4139-49. PMC: 1839947. DOI: 10.1016/j.yexcr.2006.09.012. View

13.

Chan C, Botstein D . Isolation and characterization of chromosome-gain and increase-in-ploidy mutants in yeast. Genetics. 1993; 135(3):677-91. PMC: 1205712. DOI: 10.1093/genetics/135.3.677. View

14.

Shutt D, ODorisio M, Aykin-Burns N, Spitz D . 2-deoxy-D-glucose induces oxidative stress and cell killing in human neuroblastoma cells. Cancer Biol Ther. 2010; 9(11):853-61. PMC: 3215774. DOI: 10.4161/cbt.9.11.11632. View

15.

Parrish J, Li L, Klotz K, Ledwich D, Wang X, Xue D . Mitochondrial endonuclease G is important for apoptosis in C. elegans. Nature. 2001; 412(6842):90-4. DOI: 10.1038/35083608. View

16.

Brum G, Carbone T, Still E, Correia V, Szulak K, Calianese D . N-acetylcysteine potentiates doxorubicin-induced ATM and p53 activation in ovarian cancer cells. Int J Oncol. 2012; 42(1):211-8. PMC: 3583638. DOI: 10.3892/ijo.2012.1680. View

17.

Foo T, George A, Banerjee S . PARP inhibitors in ovarian cancer: An overview of the practice-changing trials. Genes Chromosomes Cancer. 2020; 60(5):385-397. DOI: 10.1002/gcc.22935. View

18.

Kalinowska M, Garncarz W, Pietrowska M, Garrard W, Widlak P . Regulation of the human apoptotic DNase/RNase endonuclease G: involvement of Hsp70 and ATP. Apoptosis. 2005; 10(4):821-30. DOI: 10.1007/s10495-005-0410-9. View

19.

Topf U, Suppanz I, Samluk L, Wrobel L, Boser A, Sakowska P . Quantitative proteomics identifies redox switches for global translation modulation by mitochondrially produced reactive oxygen species. Nat Commun. 2018; 9(1):324. PMC: 5778013. DOI: 10.1038/s41467-017-02694-8. View

20.

Carmena M, Wheelock M, Funabiki H, Earnshaw W . The chromosomal passenger complex (CPC): from easy rider to the godfather of mitosis. Nat Rev Mol Cell Biol. 2012; 13(12):789-803. PMC: 3729939. DOI: 10.1038/nrm3474. View