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Molecular Imaging and Biology
Published in: Molecular Imaging and Biology 3/2019

01-06-2019 | Breast Cancer | Brief Article

Optical Redox Imaging Detects the Effects of DEK Oncogene Knockdown on the Redox State of MDA-MB-231 Breast Cancer Cells

Authors: Yu Wen, He N. Xu, Lisa Privette Vinnedge, Min Feng, Lin Z. Li

Published in: Molecular Imaging and Biology | Issue 3/2019

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Abstract

Purpose

Optical redox imaging (ORI), based on collecting the endogenous fluorescence of reduced nicotinamide adenine dinucleotide (NADH) and oxidized flavoproteins (Fp) containing a redox cofactor flavin adenine dinucleotide (FAD), provides sensitive indicators of cellular metabolism and redox status. ORI indices (such as NADH, FAD, and their ratio) have been under investigation as potential progression/prognosis biomarkers for cancer. Higher FAD redox ratio (i.e., FAD/(FAD + NADH)) has been associated with higher invasive/metastatic potential in tumor xenografts and cultured cells. This study is to examine whether ORI indices can respond to the modulation of oncogene DEK activities that change cancer cell invasive/metastatic potential.

Procedures

Using lentiviral shRNA, DEK gene expression was efficiently knocked down in MDA-MB-231 breast cancer cells (DEKsh). These DEKsh cells, along with scrambled shRNA-transduced control cells (NTsh), were imaged with a fluorescence microscope. In vitro invasive potential of the DEKsh cells and NTsh cells was also measured in parallel using the transwell assay.

Results

FAD and FAD redox ratios in polyclonal cells with DEKsh were significantly lower than that in NTsh control cells. Consistently, the DEKsh cells demonstrated decreased invasive potential than their non-knockdown counterparts NTsh cells.

Conclusions

This study provides direct evidence that oncogene activities could mediate ORI-detected cellular redox state.
Appendix
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Literature
1.
2.
Xu HN, Li LZ (2014) Quantitative redox imaging biomarkers for studying tissue metabolic state and its heterogeneity. J Innov Opt Health Sci 7:1430002CrossRef
3.
Alzbeta C, Dusan C (2014) Tissue fluorophores and their spectroscopic characteristics. In Fluorescence lifetime spectroscopy and imaging. CRC Press, Boca Raton, pp 47–84
4.
Chance B, Schoener B, Oshino R, Itshak F, Nakase Y (1979) Oxidation-reduction ratio studies of mitochondria in freeze-trapped samples. NADH and flavoprotein fluorescence signals. J Biol Chem 254:4764–4771
5.
Li LZ, Xu HN, Ranji M, Nioka S, Chance B (2009) Mitochondrial redox imaging for cancer diagnostic and therapeutic studies. J Innov Opt Health Sci 2:325–341CrossRefPubMedPubMedCentral
6.
Ozawa K, Chance B, Tanaka A, Iwata S, Kitai T, Ikai I (1992) Linear correlation between acetoacetate/beta-hydroxybutyrate in arterial blood and oxidized flavoprotein/reduced pyridine nucleotide in freeze-trapped human liver tissue. Biochim Biophys Acta 1138:350–352CrossRefPubMed
7.
Varone A, Xylas J, Quinn KP, Pouli D, Sridharan G, McLaughlin-Drubin ME, Alonzo C, Lee K, Munger K, Georgakoudi I (2014) Endogenous two-photon fluorescence imaging elucidates metabolic changes related to enhanced glycolysis and glutamine consumption in precancerous epithelial tissues. Cancer Res 74:3067–3075CrossRefPubMedPubMedCentral
8.
Li LZ, Sun N (2014) Autofluorescence perspective of cancer diagnostics. In: Ghukasyan V, Heikal AA (eds) Natural biomarkers for cellular metabolism: biology, techniques, and applications. CRC Press, New York, pp 273–297CrossRef
9.
10.
Li LZ, Zhou R, Xu HN, Moon L, Zhong T, Kim EJ, Qiao H, Reddy R, Leeper D, Chance B, Glickson JD (2009) Quantitative magnetic resonance and optical imaging biomarkers of melanoma metastatic potential. Proc Natl Acad Sci U S A 106:6608–6613CrossRefPubMedPubMedCentral
11.
Xu HN, Tchou J, Feng M, Zhao H, Li LZ (2016) Optical redox imaging indices discriminate human breast cancer from normal tissues. J Biomed Opt 21:114003CrossRefPubMedPubMedCentral
12.
Xu HN, Nioka S, Glickson JD, Chance B, Li LZ (2010) Quantitative mitochondrial redox imaging of breast cancer metastatic potential. J Biomed Opt 15:036010CrossRefPubMedPubMedCentral
13.
Walsh A, Cook RS, Rexer B, Arteaga CL, Skala MC (2012) Optical imaging of metabolism in HER2 overexpressing breast cancer cells. Biomed Optics Express 3:75–85CrossRef
14.
Ostrander JH, McMahon CM, Lem S et al (2010) Optical redox ratio differentiates breast cancer cell lines based on estrogen receptor status. Cancer Res 70:4759–4766CrossRef
15.
Sun N, Xu HN, Luo Q, Li LZ (2016) Potential indexing of the invasiveness of breast cancer cells by mitochondrial redox ratios. Adv Exp Med Biol 923:121–127CrossRefPubMedPubMedCentral
16.
Cairns RA, Harris IS, Mak TW (2011) Regulation of cancer cell metabolism. Nat Rev Cancer 11:85–95CrossRef
17.
18.
Xu HN, Feng M, Moon L et al (2013) Redox imaging of the p53-dependent mitochondrial redox state in colon cancer ex vivo. J Innov Opt Health Sci 6:1350016CrossRefPubMedPubMedCentral
19.
Xu HN, Nioka S, Li LZ (2013) Imaging heterogeneity in the mitochondrial redox state of premalignant pancreas in the pancreas-specific PTEN-null transgenic mouse model. Biomark Res 1:6CrossRefPubMedPubMedCentral
20.
Privette Vinnedge LM, McClaine R, Wagh PK, Wikenheiser-Brokamp KA, Waltz SE, Wells SI (2011) The human DEK oncogene stimulates beta-catenin signaling, invasion and mammosphere formation in breast cancer. Oncogene 30:2741–2752CrossRefPubMedPubMedCentral
21.
Yu L, Huang X, Zhang W, Zhao H, Wu G, Lv F, Shi L, Teng Y (2016) Critical role of DEK and its regulation in tumorigenesis and metastasis of hepatocellular carcinoma. Oncotarget 7:26844–26855PubMedPubMedCentral
22.
Privette Vinnedge LM, Benight NM, Wagh PK, Pease NA, Nashu MA, Serrano-Lopez J, Adams AK, Cancelas JA, Waltz SE, Wells SI (2015) The DEK oncogene promotes cellular proliferation through paracrine Wnt signaling in Ron receptor-positive breast cancers. Oncogene 34:2325–2336CrossRefPubMed
23.
Matrka MC, Cimperman KA, Haas SR, Guasch G, Ehrman LA, Waclaw RR, Komurov K, Lane A, Wikenheiser-Brokamp KA, Wells SI (2018) Dek overexpression in murine epithelia increases overt esophageal squamous cell carcinoma incidence. PLoS Genet 14:e1007227CrossRefPubMedPubMedCentral
24.
Liu G, Xiong D, Zeng J et al (2017) Prognostic role of DEK in human solid tumors: a meta-analysis. Oncotarget 8:98985–98992PubMedPubMedCentral
25.
Ying G, Wu Y (2015) DEK: a novel early screening and prognostic marker for breast cancer. Mol Med Rep 12:7491–7495CrossRefPubMed
26.
Lin Z, Xu HN, Wang Y, Floros J, Li LZ (2018) Differential expression of PGC1alpha in intratumor redox subpopulations of breast cancer. Adv Exp Med Biol 1072:177–181CrossRefPubMedPubMedCentral
27.
Wise-Draper TM, Allen HV, Thobe MN, Jones EE, Habash KB, Munger K, Wells SI (2005) The human DEK proto-oncogene is a senescence inhibitor and an upregulated target of high-risk human papillomavirus E7. J Virol 79:14309–14317CrossRefPubMedPubMedCentral
28.
Pate KT, Stringari C, Sprowl-Tanio S, Wang K, TeSlaa T, Hoverter NP, McQuade M, Garner C, Digman MA, Teitell MA, Edwards RA, Gratton E, Waterman ML (2014) Wnt signaling directs a metabolic program of glycolysis and angiogenesis in colon cancer. EMBO J 33:1454–1473CrossRef
29.
Matrka MC, Watanabe M, Muraleedharan R, Lambert PF, Lane AN, Romick-Rosendale LE, Wells SI (2017) Overexpression of the human DEK oncogene reprograms cellular metabolism and promotes glycolysis. PLoS One 12:e0177952CrossRefPubMedPubMedCentral
30.
Walsh AJ, Cook RS, Sanders ME, Aurisicchio L, Ciliberto G, Arteaga CL, Skala MC (2014) Quantitative optical imaging of primary tumor organoid metabolism predicts drug response in breast cancer. Cancer Res 74:5184–5194CrossRefPubMedPubMedCentral
31.
Alhallak K, Rebello LG, Muldoon TJ, Quinn KP, Rajaram N (2016) Optical redox ratio identifies metastatic potential-dependent changes in breast cancer cell metabolism. Biomed Opt Express 7:4364–4374CrossRefPubMedPubMedCentral
32.
Santidrian AF, Matsuno-Yagi A, Ritland M, Seo BB, LeBoeuf SE, Gay LJ, Yagi T, Felding-Habermann B (2013) Mitochondrial complex I activity and NAD+/NADH balance regulate breast cancer progression. J Clin Invest 123:1068–1081CrossRefPubMedPubMedCentral
33.
Kunz WS (1988) Evaluation of electron-transfer flavoprotein and alpha-lipoamide dehydrogenase redox states by two-channel fluorimetry and its application to the investigation of beta-oxidation. Biochim Biophys Acta 932:8–16CrossRefPubMed
34.
Kunz WS, Gellerich FN (1993) Quantification of the content of fluorescent flavoproteins in mitochondria from liver, kidney cortex, skeletal muscle, and brain. Biochem Med Metab Biol 50:103–110CrossRef
35.
Rehman AU, Anwer AG, Gosnell ME, Mahbub SB, Liu G, Goldys EM (2017) Fluorescence quenching of free and bound NADH in HeLa cells determined by hyperspectral imaging and unmixing of cell autofluorescence. Biomed Opt Express 8:1488–1498CrossRefPubMedPubMedCentral
36.
Banerjee R (2008) Redox biochemistry. John Wiley & Sons, Hoboken
37.
Holmgren A (1989) Thioredoxin and glutaredoxin systems. J Biol Chem 264:13963–13966PubMed
38.
Metadata
Title
Optical Redox Imaging Detects the Effects of DEK Oncogene Knockdown on the Redox State of MDA-MB-231 Breast Cancer Cells
Authors
Yu Wen
He N. Xu
Lisa Privette Vinnedge
Min Feng
Lin Z. Li
Publication date
01-06-2019
Publisher
Springer International Publishing
Published in
Molecular Imaging and Biology / Issue 3/2019
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI
https://doi.org/10.1007/s11307-019-01321-w

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