Skip to main content

Advertisement

SpringerLink
Log in

Identification of the inhibitor of growth protein 4 (ING4) as a potential target in prostate cancer therapy

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

INhibitor of Growth protein 4 (ING4) is a potential chromatin modifier that has been implicated in several cancer-related processes. However, the role of ING4 in prostate cancer (PC) is largely unknown. This study aimed to assess ING4’s role in global transcriptional regulation in PC cells to identify potential cellular processes associated with ING4 loss. RNA-Seq using next-generation sequencing (NGS) was used to identify altered genes in LNCaP PC cells following ING4 depletion. Ingenuity pathways analysis (IPA®) was applied to the data to highlight candidates, ING4-regulated pathways, networks and cellular processes. Selected genes were validated using RT-qPCR. RNA-Seq of LNCaP cells revealed a total of 159 differentially expressed genes (fold change ≥ 1.5 or ≤ − 1.5, FDR ≤ 0.05) following ING4 knockdown. RT-qPCR used to validate the expression level of selected genes was in agreement with RNA-Seq results. Key genes, unique pathways, and biological networks were identified using IPA® analysis. This is the first report of global gene regulation in PC cells by ING4. The resultant differential expression profile revealed the potential role of ING4 in PC pathogenesis possibly through modulation of key genes, pathways and biological networks that are central drivers of the disease. Collectively, these findings shed light on a novel transcriptional regulator of PC that ultimately may influence the disease progression and as a potential target in the disease therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

References

  1. Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. CA Cancer J Clin 68(1):7–30. https://doi.org/10.3322/caac.21442

    Article  PubMed  Google Scholar 

  2. Copeland BT, Pal SK, Bolton EC, Jones JO (2018) The androgen receptor malignancy shift in prostate cancer. Prostate 78(7):521–531. https://doi.org/10.1002/pros.23497

    Article  CAS  PubMed  Google Scholar 

  3. Brand LJ, Dehm SM (2013) Androgen receptor gene rearrangements: new perspectives on prostate cancer progression. Curr Drug Targets 14(4):441–449

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Luo J, Attard G, Balk SP, Bevan C, Burnstein K, Cato L, Cherkasov A, De Bono JS, Dong Y, Gao AC, Gleave M, Heemers H, Kanayama M, Kittler R, Lang JM, Lee RJ, Logothetis CJ, Matusik R, Plymate S, Sawyers CL, Selth LA, Soule H, Tilley W, Weigel NL, Zoubeidi A, Dehm SM, Raj GV (2018) Role of androgen receptor variants in prostate cancer: report from the 2017 mission androgen receptor variants meeting. Eur Urol 73(5):715–723. https://doi.org/10.1016/j.eururo.2017.11.038

    Article  PubMed  Google Scholar 

  5. Kohli M, Ho Y, Hillman DW, Van Etten JL, Henzler C, Yang R, Sperger JM, Li Y, Tseng E, Hon T, Clark T, Tan W, Carlson RE, Wang L, Sicotte H, Thai H, Jimenez R, Huang H, Vedell PT, Eckloff BW, Quevedo JF, Pitot HC, Costello BA, Jen J, Wieben ED, Silverstein KAT, Lang JM, Wang L, Dehm SM (2017) Androgen receptor variant AR-V9 is coexpressed with AR-V7 in prostate cancer metastases and predicts abiraterone resistance. Clin Cancer Res 23(16):4704–4715. https://doi.org/10.1158/1078-0432.CCR-17-0017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Chang CY, McDonnell DP (2005) Androgen receptor-cofactor interactions as targets for new drug discovery. Trends Pharmacol Sci 26(5):225–228. https://doi.org/10.1016/j.tips.2005.03.002

    Article  CAS  PubMed  Google Scholar 

  7. Barfeld SJ, Urbanucci A, Itkonen HM, Fazli L, Hicks JL, Thiede B, Rennie PS, Yegnasubramanian S, DeMarzo AM, Mills IG (2017) c-Myc antagonises the transcriptional activity of the androgen receptor in prostate cancer affecting key gene Networks. EBioMedicine 18:83–93. https://doi.org/10.1016/j.ebiom.2017.04.006

    Article  PubMed  PubMed Central  Google Scholar 

  8. Kivinummi K, Urbanucci A, Leinonen K, Tammela TLJ, Annala M, Isaacs WB, Bova GS, Nykter M, Visakorpi T (2017) The expression of AURKA is androgen regulated in castration-resistant prostate cancer. Sci Rep 7(1):17978. https://doi.org/10.1038/s41598-017-18210-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Zabalza CV, Adam M, Burdelski C, Wilczak W, Wittmer C, Kraft S, Krech T, Steurer S, Koop C, Hube-Magg C, Graefen M, Heinzer H, Minner S, Simon R, Sauter G, Schlomm T, Tsourlakis MC (2015) HOXB13 overexpression is an independent predictor of early PSA recurrence in prostate cancer treated by radical prostatectomy. Oncotarget 6(14):12822–12834. https://doi.org/10.18632/oncotarget.3431

    Article  PubMed  PubMed Central  Google Scholar 

  10. Burdelski C, Strauss C, Tsourlakis MC, Kluth M, Hube-Magg C, Melling N, Lebok P, Minner S, Koop C, Graefen M, Heinzer H, Wittmer C, Krech T, Sauter G, Wilczak W, Simon R, Schlomm T, Steurer S (2015) Overexpression of thymidylate synthase (TYMS) is associated with aggressive tumor features and early PSA recurrence in prostate cancer. Oncotarget 6(10):8377–8387

    Article  PubMed  PubMed Central  Google Scholar 

  11. Kim S, Chin K, Gray JW, Bishop JM (2004) A screen for genes that suppress loss of contact inhibition: identification of ING4 as a candidate tumor suppressor gene in human cancer. Proc Natl Acad Sci USA 101(46):16251–16256. https://doi.org/10.1073/pnas.0407158101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Guerillon C, Bigot N, Pedeux R (2014) The ING tumor suppressor genes: status in human tumors. Cancer Lett 345(1):1–16. https://doi.org/10.1016/j.canlet.2013.11.016

    Article  CAS  PubMed  Google Scholar 

  13. Li M, Zhu Y, Zhang H, Li L, He P, Xia H, Zhang Y, Mao C (2014) Delivery of inhibitor of growth 4 (ING4) gene significantly inhibits proliferation and invasion and promotes apoptosis of human osteosarcoma cells. Sci Rep 4:7380. https://doi.org/10.1038/srep07380

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Li J, Martinka M, Li G (2008) Role of ING4 in human melanoma cell migration, invasion and patient survival. Carcinogenesis 29(7):1373–1379. https://doi.org/10.1093/carcin/bgn086

    Article  CAS  PubMed  Google Scholar 

  15. Garkavtsev I, Kozin SV, Chernova O, Xu L, Winkler F, Brown E, Barnett GH, Jain RK (2004) The candidate tumour suppressor protein ING4 regulates brain tumour growth and angiogenesis. Nature 428(6980):328–332. https://doi.org/10.1038/nature02329

    Article  CAS  PubMed  Google Scholar 

  16. Tapia C, Zlobec I, Schneider S, Kilic E, Guth U, Bubendorf L, Kim S (2011) Deletion of the inhibitor of growth 4 (ING4) tumor suppressor gene is prevalent in human epidermal growth factor 2 (HER2)-positive breast cancer. Hum Pathol 42(7):983–990. https://doi.org/10.1016/j.humpath.2010.10.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Li S, Fan T, Liu H, Chen J, Qin C, Ren X (2013) Tumor suppressor ING4 overexpression contributes to proliferation and invasion inhibition in gastric carcinoma by suppressing the NF-kappaB signaling pathway. Mol Biol Rep 40(10):5723–5732. https://doi.org/10.1007/s11033-013-2675-3

    Article  CAS  PubMed  Google Scholar 

  18. Wang QS, Li M, Zhang LY, Jin Y, Tong DD, Yu Y, Bai J, Huang Q, Liu FL, Liu A, Lee KY, Fu SB (2010) Down-regulation of ING4 is associated with initiation and progression of lung cancer. Histopathology 57(2):271–281. https://doi.org/10.1111/j.1365-2559.2010.03623.x

    Article  PubMed  PubMed Central  Google Scholar 

  19. Ren X, Liu H, Zhang M, Wang M, Ma S (2016) Co-expression of ING4 and P53 enhances hypopharyngeal cancer chemosensitivity to cisplatin in vivo. Mol Med Rep 14(3):2431–2438. https://doi.org/10.3892/mmr.2016.5552

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Cao L, Chen S, Zhang C, Chen C, Lu N, Jiang Y, Cai Y, Yin Y, Xu J (2015) ING4 enhances paclitaxel’s effect on colorectal cancer growth in vitro and in vivo. Int J Clin Exp Pathol 8(3):2919–2927

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Shiseki M, Nagashima M, Pedeux RM, Kitahama-Shiseki M, Miura K, Okamura S, Onogi H, Higashimoto Y, Appella E, Yokota J, Harris CC (2003) p29ING4 and p28ING5 bind to p53 and p300, and enhance p53 activity. Cancer Res 63(10):2373–2378

    CAS  PubMed  Google Scholar 

  22. Moreno A, Palacios A, Orgaz JL, Jimenez B, Blanco FJ, Palmero I (2010) Functional impact of cancer-associated mutations in the tumor suppressor protein ING4. Carcinogenesis 31(11):1932–1938. https://doi.org/10.1093/carcin/bgq171

    Article  CAS  PubMed  Google Scholar 

  23. Doyon Y, Cayrou C, Ullah M, Landry AJ, Cote V, Selleck W, Lane WS, Tan S, Yang XJ, Cote J (2006) ING tumor suppressor proteins are critical regulators of chromatin acetylation required for genome expression and perpetuation. Mol Cell 21(1):51–64. https://doi.org/10.1016/j.molcel.2005.12.007

    Article  CAS  PubMed  Google Scholar 

  24. Hung T, Binda O, Champagne KS, Kuo AJ, Johnson K, Chang HY, Simon MD, Kutateladze TG, Gozani O (2009) ING4 mediates crosstalk between histone H3 K4 trimethylation and H3 acetylation to attenuate cellular transformation. Mol Cell 33(2):248–256. https://doi.org/10.1016/j.molcel.2008.12.016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Palacios A, Munoz IG, Pantoja-Uceda D, Marcaida MJ, Torres D, Martin-Garcia JM, Luque I, Montoya G, Blanco FJ (2008) Molecular basis of histone H3K4me3 recognition by ING4. J Biol Chem 283(23):15956–15964. https://doi.org/10.1074/jbc.M710020200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Hou Y, Zhang Z, Xu Q, Wang H, Xu Y, Chen K (2014) Inhibitor of growth 4 induces NFkappaB/p65 ubiquitin-dependent degradation. Oncogene 33(15):1997–2003. https://doi.org/10.1038/onc.2013.135

    Article  CAS  PubMed  Google Scholar 

  27. Nozell S, Laver T, Moseley D, Nowoslawski L, De Vos M, Atkinson GP, Harrison K, Nabors LB, Benveniste EN (2008) The ING4 tumor suppressor attenuates NF-kappaB activity at the promoters of target genes. Mol Cell Biol 28(21):6632–6645. https://doi.org/10.1128/MCB.00697-08

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Coles AH, Gannon H, Cerny A, Kurt-Jones E, Jones SN (2010) Inhibitor of growth-4 promotes IkappaB promoter activation to suppress NF-kappaB signaling and innate immunity. Proc Natl Acad Sci USA 107(25):11423–11428. https://doi.org/10.1073/pnas.0912116107

    Article  PubMed  PubMed Central  Google Scholar 

  29. Ythier D, Larrieu D, Brambilla C, Brambilla E, Pedeux R (2008) The new tumor suppressor genes ING: genomic structure and status in cancer. Int J Cancer 123(7):1483–1490. https://doi.org/10.1002/ijc.23790

    Article  CAS  PubMed  Google Scholar 

  30. Zhang X, Wang KS, Wang ZQ, Xu LS, Wang QW, Chen F, Wei DZ, Han ZG (2005) Nuclear localization signal of ING4 plays a key role in its binding to p53. Biochem Biophys Res Commun 331(4):1032–1038. https://doi.org/10.1016/j.bbrc.2005.04.023

    Article  CAS  PubMed  Google Scholar 

  31. Berger PL, Frank SB, Schulz VV, Nollet EA, Edick MJ, Holly B, Chang TT, Hostetter G, Kim S, Miranti CK (2014) Transient induction of ING4 by Myc drives prostate epithelial cell differentiation and its disruption drives prostate tumorigenesis. Cancer Res 74(12):3357–3368. https://doi.org/10.1158/0008-5472.CAN-13-3076

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Lou C, Jiang S, Guo X, Dong XS (2012) ING4 is negatively correlated with microvessel density in colon cancer. Tumour Biol 33(6):2357–2364. https://doi.org/10.1007/s13277-012-0498-9

    Article  CAS  PubMed  Google Scholar 

  33. Liu Y, Yu L, Wang Y, Zhang Y, Wang Y, Zhang G (2012) Expression of tumor suppressor gene ING4 in ovarian carcinoma is correlated with microvessel density. J Cancer Res Clin Oncol 138(4):647–655. https://doi.org/10.1007/s00432-011-1099-5

    Article  CAS  PubMed  Google Scholar 

  34. Andrews S FastQC A Quality Control tool for High Throughput Sequence Data. http://www.bioinformatics.babraham.ac.uk/projects/fastqc/. Accessed 10 May 2019

  35. Martin M (2011) Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet J 7(1):3. https://doi.org/10.14806/ej.17.1.200

    Article  Google Scholar 

  36. Galore KFT A wrapper tool around Cutadapt and FastQC to consistently apply quality and adapter trimming to FastQ files, with some extra functionality for MspI-digested RRBS-type (Reduced Representation Bisufite-Seq) libraries. http://www.bioinformatics.babraham.ac.uk/projects/trim_galore/. Accessed 10 May 2019

  37. Kim D, Pertea G, Trapnell C, Pimentel H, Kelley R, Salzberg SL (2013) TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol 14(4):R36. https://doi.org/10.1186/gb-2013-14-4-r36

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, Batut P, Chaisson M, Gingeras TR (2013) STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29(1):15–21. https://doi.org/10.1093/bioinformatics/bts635

    Article  CAS  PubMed  Google Scholar 

  39. Anders S, Pyl PT, Huber W (2015) HTSeq–a Python framework to work with high-throughput sequencing data. Bioinformatics 31(2):166–169. https://doi.org/10.1093/bioinformatics/btu638

    Article  CAS  PubMed  Google Scholar 

  40. Love MI, Huber W, Anders S (2014) Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 15(12):550. https://doi.org/10.1186/s13059-014-0550-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. O’Malley BW, Malovannaya A, Qin J (2012) Minireview: nuclear receptor and coregulator proteomics–2012 and beyond. Mol Endocrinol 26(10):1646–1650. https://doi.org/10.1210/me.2012-1114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Zhang L, Wang Y, Zhang F, Wang Y, Zhang Q (2012) Correlation between tumor suppressor inhibitor of growth family member 4 expression and microvessel density in breast cancer. Hum Pathol 43(10):1611–1617. https://doi.org/10.1016/j.humpath.2011.11.018

    Article  CAS  PubMed  Google Scholar 

  43. Cai L, Li X, Zheng S, Wang Y, Wang Y, Li H, Yang J, Sun J (2009) Inhibitor of growth 4 is involved in melanomagenesis and induces growth suppression and apoptosis in melanoma cell line M14. Melanoma Res 19(1):1–7. https://doi.org/10.1097/CMR.0b013e32831bc42f

    Article  CAS  PubMed  Google Scholar 

  44. Krajewska M, Krajewski S, Epstein JI, Shabaik A, Sauvageot J, Song K, Kitada S, Reed JC (1996) Immunohistochemical analysis of bcl-2, bax, bcl-X, and mcl-1 expression in prostate cancers. Am J Pathol 148(5):1567–1576

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Beham AW, Sarkiss M, Brisbay S, Tu SM, von Eschenbach AC, McDonnell TJ (1998) Molecular correlates of bcl-2-enhanced growth following androgen-ablation in prostate carcinoma cells in vivo. Int J Mol Med 1(6):953–959. https://doi.org/10.3892/ijmm.1.6.953

    Article  CAS  PubMed  Google Scholar 

  46. Luk IY, Reehorst CM, Mariadason JM (2018) ELF3, ELF5, EHF and SPDEF Transcription factors in tissue homeostasis and cancer. Molecules. https://doi.org/10.3390/molecules23092191

    Article  PubMed  PubMed Central  Google Scholar 

  47. Yao B, Zhao J, Li Y, Li H, Hu Z, Pan P, Zhang Y, Du E, Liu R, Xu Y (2015) Elf5 inhibits TGF-beta-driven epithelial-mesenchymal transition in prostate cancer by repressing SMAD3 activation. Prostate 75(8):872–882. https://doi.org/10.1002/pros.22970

    Article  CAS  PubMed  Google Scholar 

  48. Li K, Guo Y, Yang X, Zhang Z, Zhang C, Xu Y (2017) ELF5-mediated ar activation regulates prostate cancer progression. Sci Rep 7:42759. https://doi.org/10.1038/srep42759

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Okamoto Y, Ozaki T, Miyazaki K, Aoyama M, Miyazaki M, Nakagawara A (2003) UbcH10 is the cancer-related E2 ubiquitin-conjugating enzyme. Cancer Res 63(14):4167–4173

    CAS  PubMed  Google Scholar 

  50. Xie C, Powell C, Yao M, Wu J, Dong Q (2014) Ubiquitin-conjugating enzyme E2C: a potential cancer biomarker. Int J Biochem Cell Biol 47:113–117. https://doi.org/10.1016/j.biocel.2013.11.023

    Article  CAS  PubMed  Google Scholar 

  51. Chaturvedi MM, Sung B, Yadav VR, Kannappan R, Aggarwal BB (2011) NF-kappaB addiction and its role in cancer: ‘one size does not fit all’. Oncogene 30(14):1615–1630. https://doi.org/10.1038/onc.2010.566

    Article  CAS  PubMed  Google Scholar 

  52. Byron SA, Min E, Thal TS, Hostetter G, Watanabe AT, Azorsa DO, Little TH, Tapia C, Kim S (2012) Negative regulation of NF-kappaB by the ING4 tumor suppressor in breast cancer. PLoS ONE 7(10):e46823. https://doi.org/10.1371/journal.pone.0046823

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Saxon ML, Zhao X, Black JD (1994) Activation of protein kinase C isozymes is associated with post-mitotic events in intestinal epithelial cells in situ. J Cell Biol 126(3):747–763

    Article  CAS  PubMed  Google Scholar 

  54. Frey MR, Saxon ML, Zhao X, Rollins A, Evans SS, Black JD (1997) Protein kinase C isozyme-mediated cell cycle arrest involves induction of p21(waf1/cip1) and p27(kip1) and hypophosphorylation of the retinoblastoma protein in intestinal epithelial cells. J Biol Chem 272(14):9424–9435

    Article  CAS  PubMed  Google Scholar 

  55. Oster H, Leitges M (2006) Protein kinase C alpha but not PKCzeta suppresses intestinal tumor formation in ApcMin/+ mice. Cancer Res 66(14):6955–6963. https://doi.org/10.1158/0008-5472.CAN-06-0268

    Article  CAS  PubMed  Google Scholar 

  56. Uchi Y, Takeuchi H, Matsuda S, Saikawa Y, Kawakubo H, Wada N, Takahashi T, Nakamura R, Fukuda K, Omori T, Kitagawa Y (2016) CXCL12 expression promotes esophageal squamous cell carcinoma proliferation and worsens the prognosis. BMC Cancer 16:514. https://doi.org/10.1186/s12885-016-2555-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Boimel PJ, Smirnova T, Zhou ZN, Wyckoff J, Park H, Coniglio SJ, Qian BZ, Stanley ER, Cox D, Pollard JW, Muller WJ, Condeelis J, Segall JE (2012) Contribution of CXCL12 secretion to invasion of breast cancer cells. Breast Cancer Res 14(1):R23. https://doi.org/10.1186/bcr3108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Duffy MJ, Maguire TM, Hill A, McDermott E, O’Higgins N (2000) Metalloproteinases: role in breast carcinogenesis, invasion and metastasis. Breast Cancer Res 2(4):252–257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674. https://doi.org/10.1016/j.cell.2011.02.013

    Article  CAS  PubMed  Google Scholar 

  60. You J, Chen W, Chen J, Zheng Q, Dong J, Zhu Y (2018) The oncogenic role of ARG1 in progression and metastasis of hepatocellular carcinoma. Biomed Res Int. https://doi.org/10.1155/2018/2109865

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We would like to thank Dr. Daniel Frigo (The University of Texas, MD Anderson Cancer Center, Houston, TX)) for his constructive comments and technical support. This study was supported by WV-INBRE Genomic Core Grant # P20GM103434 and DPAS-UCSOP internal fund.

Author information

Authors and Affiliations

  1. Department of Pharmaceutical and Administrative Sciences, University of Charleston School of Pharmacy, 2300 MacCorkle Ave SE, Charleston, WV, 25304, USA

    Aymen Shatnawi & Tamer Fandy

  2. Department of Mathematics and Computer Sciences, West Virginia State University, W729, Wallace Hall, Institute, WV, 25112, USA

    Sridhar A. Malkaram

  3. Department of Orthopedic Surgery, Baylor College of Medicine, Houston, TX, 77030, USA

    Efrosini Tsouko

Authors
  1. Aymen Shatnawi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sridhar A. Malkaram
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tamer Fandy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Efrosini Tsouko
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Aymen Shatnawi.

Ethics declarations

Conflict of interest

Authors declare that they have no conflict of interest, financial or otherwise regarding the content of the manuscript.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 22 kb)

Supplementary material 2 (DOCX 22 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shatnawi, A., Malkaram, S.A., Fandy, T. et al. Identification of the inhibitor of growth protein 4 (ING4) as a potential target in prostate cancer therapy. Mol Cell Biochem 464, 153–167 (2020). https://doi.org/10.1007/s11010-019-03657-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-019-03657-x

Keywords

Search

Navigation