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Cited by 18Head and Neck Cancer StudiesCancer-related Molecular PathwaysCancer Mechanisms and Therapy

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Cell division cycle 7 is a potential therapeutic target in oral squamous cell carcinoma and is regulated by E2F1

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Jin, Shufang, Ma, Hailong, Yang, Wenyi, Ju, Houyu, Wang, Lizhen, Zhang, Zhiyuan·2018·Journal of Molecular Medicine
DOI 10.1007/s00109-018-1636-7
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Abstract

Cell division cycle 7 (Cdc7) plays important roles in the regulation of the initiation of DNA replication throughout S phase. Whether inhibition of Cdc7 has a direct antitumour effect in oral squamous cell carcinoma (OSCC) remains unclear. In this study, XL413, a novel Cdc7 inhibitor, markedly inhibited the viability of OSCC cells but not that of non-tumour primary cells. There was a synergistic effect between XL413 and DNA-damaging agents (e.g. cisplatin and 5-fluorouracil) on OSCC in vitro and in vivo. Moreover, XL413 exhibited a notable antitumour effect on OSCC patients with high Cdc7 expression in mini patient-derived xenografts model. The proliferation was significantly inhibited in OSCC cells after Cdc7 silencing. Cdc7 knockdown significantly induced apoptosis in OSCC cell lines. Furthermore, we demonstrated that Cdc7 was overexpressed and transcriptionally regulated by E2F1 in OSCC by using chromatin immunoprecipitation and luciferase assays. Our results reveal that XL413 has an excellent antitumour effect in OSCC. Importantly, it does not inhibit the proliferation of non-tumour cells. These findings suggest that the overexpression of Cdc7 promotes progression in OSCC and that inhibition of Cdc7 is a very promising therapy for OSCC patients.

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  • Many of the genes in CisSig have been denoted as possible therapeutic targets in a variety of epithelial-based cancers.

    “Furthermore, many of the genes have been denoted as possible therapeutic targets in a variety of epithelial-based cancers, such as CDC7 in oral squamous carcinoma30 and liver cancer31, ATP1B3 in gastric cancer32, and FKBP14 in ovarian cancer33.”

    From Exploiting convergent phenotypes to derive a pan-cancer cisplatin response gene expression signature (2023) · cites this paper as [30]

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Research works printed but not linked: 37

  1. Chinn SB, Myers JN (2015) Oral cavity carcinoma: current management, controversies, and future directions. J Clin Oncol 33(29):3269–3276 · DOI
  2. Bester A, Roniger M, Oren Y, Im M, Sarni D, Chaoat M, Bensimon A, Zamir G, Shewach D, Kerem B (2011) Nucleotide deficiency promotes genomic instability in early stages of cancer development. Cell 145(3):435–446 · DOI · Paper page
  3. Dobbelstein M, Sorensen CS (2015) Exploiting replicative stress to treat cancer. Nat Rev Drug Discov 14(6):405–423 · DOI
  4. Kumagai H, Sato N, Yamada M, Mahony D, Seghezzi W, Lees E, Arai K, Masai H (1999) A novel growth- and cell cycle-regulated protein, ASK, activates human Cdc7-related kinase and is essential for G1/S transition in mammalian cells. Mol Cell Biol 19(7):5083–5095 · DOI
  5. Chen L, Luo C, Shen L, Liu Y, Wang Q, Zhang C, Guo R, Zhang Y, Xie Z, Wei N, Wu W, Han J, Feng Y (2017) SRSF1 prevents DNA damage and promotes tumorigenesis through regulation of DBF4B pre-mRNA splicing. Cell Rep 21(12):3406–3413 · DOI
  6. Yamada M, Masai H, Bartek J (2014) Regulation and roles of Cdc7 kinase under replication stress. Cell Cycle 13(12):1859–1866 · DOI
  7. Yamada M, Sato N, Taniyama C, Ohtani K, Arai K, Masai H (2002) A 63-base pair DNA segment containing an Sp1 site but not a canonical E2F site can confer growth-dependent and E2F-mediated transcriptional stimulation of the human ASK gene encoding the regulatory subunit for human Cdc7-related kinase. J Biol Chem 277(31):27668–27681 · DOI
  8. Bonte D, Lindvall C, Liu H, Dykema K, Furge K, Weinreich M (2008) Cdc7-Dbf4 kinase overexpression in multiple cancers and tumor cell lines is correlated with p53 inactivation. Neoplasia 10(9):920–931 · DOI
  9. Rodriguez-Acebes S, Proctor I, Loddo M, Wollenschlaeger A, Rashid M, Falzon M, Prevost AT, Sainsbury R, Stoeber K, Williams GH (2010) Targeting DNA replication before it starts: Cdc7 as a therapeutic target in p53-mutant breast cancers. Am J Pathol 177(4):2034–2045 · DOI
  10. Kulkarni AA, Kingsbury SR, Tudzarova S, Hong HK, Loddo M, Rashid M, Rodriguez-Acebes S, Prevost AT, Ledermann JA, Stoeber K, Williams GH (2009) Cdc7 kinase is a predictor of survival and a novel therapeutic target in epithelial ovarian carcinoma. Clin Cancer Res 15(7):2417–2425 · DOI
  11. Hou Y, Wang HQ, Ba Y (2012) High expression of cell division cycle 7 protein correlates with poor prognosis in patients with diffuse large B-cell lymphoma. Med Oncol 29(5):3498–3503 · DOI
  12. Cheng AN, Jiang SS, Fan CC, Lo YK, Kuo CY, Chen CH, Liu YL, Lee CC, Chen WS, Huang TS, Wang TY, Lee AY (2013) Increased Cdc7 expression is a marker of oral squamous cell carcinoma and overexpression of Cdc7 contributes to the resistance to DNA-damaging agents. Cancer Lett 337(2):218–225 · DOI
  13. Montagnoli A, Moll J, Colotta F (2010) Targeting cell division cycle 7 kinase: a new approach for cancer therapy. Clin Cancer Res 16(18):4503–4508 · DOI
  14. Toruner GA, Ulger C, Alkan M, Galante AT, Rinaggio J, Wilk R, Tian B, Soteropoulos P, Hameed MR, Schwalb MN, Dermody JJ (2004) Association between gene expression profile and tumor invasion in oral squamous cell carcinoma. Cancer Genet Cytogenet 154(1):27–35 · DOI
  15. Yap L, Jenei V, Robinson C, Moutasim K, Benn T, Threadgold S, Lopes V, Wei W, Thomas G, Paterson I (2009) Upregulation of Eps8 in oral squamous cell carcinoma promotes cell migration and invasion through integrin-dependent Rac1 activation. Oncogene 28(27):2524–2534 · DOI
  16. Gao J, Aksoy B, Dogrusoz U, Dresdner G, Gross B, Sumer S, Sun Y, Jacobsen A, Sinha R, Larsson E, Cerami E, Sander C, Schultz N (2013) Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal 6(269):pl1 · DOI · Paper page
  17. Cerami E, Gao J, Dogrusoz U, Gross B, Sumer S, Aksoy B, Jacobsen A, Byrne C, Heuer M, Larsson E, Antipin Y, Reva B, Goldberg A, Sander C, Schultz N (2012) The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov 2(5):401–404 · DOI · Paper page
  18. Jin SF, Ma HL, Liu ZL, Fu ST, Zhang CP, He Y (2015) XL413, a cell division cycle 7 kinase inhibitor enhanced the anti-fibrotic effect of pirfenidone on TGF-beta1-stimulated C3H10T1/2 cells via Smad2/4. Exp Cell Res 339(2):289–299 · DOI
  19. Ma HL, Jin SF, Ju WT, Fu Y, Tu YY, Wang LZ, Jiang L, Zhang ZY, Zhong LP (2017) Stathmin is overexpressed and regulated by mutant p53 in oral squamous cell carcinoma. J Exp Clin Cancer Res 36(1):109 · DOI
  20. Ma H, Jin S, Yang W, Zhou G, Zhao M, Fang S, Zhang Z, Hu J (2018) Interferon-alpha enhances the antitumour activity of EGFR-targeted therapies by upregulating RIG-I in head and neck squamous cell carcinoma. Br J Cancer 118(4):509–521 · DOI
  21. Bruzzese F, Di Gennaro E, Avallone A, Pepe S, Arra C, Caraglia M, Tagliaferri P, Budillon A (2006) Synergistic antitumor activity of epidermal growth factor receptor tyrosine kinase inhibitor gefitinib and IFN-alpha in head and neck cancer cells in vitro and in vivo. Clin Cancer Res 12(2):617–625 · DOI
  22. Ma H, Jin S, Yang W, Tian Z, Liu S, Wang Y, Zhou G, Zhao M, Gvetadze S, Zhang Z, Hu J (2017) Interferon-alpha promotes the expression of cancer stem cell markers in oral squamous cell carcinoma. J Cancer 8(12):2384–2393 · DOI
  23. Tanaka C, Uzawa K, Shibahara T, Yokoe H, Noma H, Tanzawa H (2003) Expression of an inhibitor of apoptosis, survivin, in oral carcinogenesis. J Dent Res 82(8):607–611 · DOI
  24. Zhang G, Chen T, Hargreaves R, Sur C, Williams D (2008) Bioluminescence imaging of hollow fibers in living animals: its application in monitoring molecular pathways. Nat Protoc 3(5):891–899 · DOI
  25. Koltun ES, Tsuhako AL, Brown DS, Aay N, Arcalas A, Chan V, Du H, Engst S, Ferguson K, Franzini M, Galan A, Holst CR, Huang P, Kane B, Kim MH, Li J, Markby D, Mohan M, Noson K, Plonowski A, Richards SJ, Robertson S, Shaw K, Stott G, Stout TJ, Young J, Yu P, Zaharia CA, Zhang W, Zhou P, Nuss JM, Xu W, Kearney PC (2012) Discovery of XL413, a potent and selective CDC7 inhibitor. Bioorg Med Chem Lett 22(11):3727–3731 · DOI
  26. Rainey M, Quachthithu H, Gaboriau D, Santocanale C (2017) DNA replication dynamics and cellular responses to ATP competitive CDC7 kinase inhibitors. ACS Chem Biol 12(7):1893–1902 · DOI
  27. Li W, Zhao XL, Shang SQ, Shen HQ, Chen X (2015) Dual inhibition of Cdc7 and Cdk9 by PHA-767491 suppresses hepatocarcinoma synergistically with 5-fluorouracil. Curr Cancer Drug Targets 15(3):196–204 · DOI
  28. Erbayraktar Z, Alural B, Erbayraktar RS, Erkan EP (2016) Cell division cycle 7-kinase inhibitor PHA-767491 hydrochloride suppresses glioblastoma growth and invasiveness. Cancer Cell Int 16:88. https://doi.org/10.1186/s12935-016-0364-8 · DOI
  29. Montagnoli A, Valsasina B, Croci V, Menichincheri M, Rainoldi S, Marchesi V, Tibolla M, Tenca P, Brotherton D, Albanese C, Patton V, Alzani R, Ciavolella A, Sola F, Molinari A, Volpi D, Avanzi N, Fiorentini F, Cattoni M, Healy S, Ballinari D, Pesenti E, Isacchi A, Moll J, Bensimon A, Vanotti E, Santocanale C (2008) A Cdc7 kinase inhibitor restricts initiation of DNA replication and has antitumor activity. Nat Chem Biol 4(6):357–365 · DOI
  30. Natoni A, Murillo LS, Kliszczak AE, Catherwood MA, Montagnoli A, Samali A, O’Dwyer M, Santocanale C (2011) Mechanisms of action of a dual Cdc7/Cdk9 kinase inhibitor against quiescent and proliferating CLL cells. Mol Cancer Ther 10(9):1624–1634 · DOI
  31. Jiang W, McDonald D, Hope TJ, Hunter T (1999) Mammalian Cdc7-Dbf4 protein kinase complex is essential for initiation of DNA replication. EMBO J 18(20):5703–5713 · DOI
  32. Montagnoli A, Tenca P, Sola F, Carpani D, Brotherton D, Albanese C, Santocanale C (2004) Cdc7 inhibition reveals a p53-dependent replication checkpoint that is defective in cancer cells. Cancer Res 64(19):7110–7116 · DOI
  33. Tudzarova S, Trotter M, Wollenschlaeger A, Mulvey C, Godovac-Zimmermann J, Williams G, Stoeber K (2010) Molecular architecture of the DNA replication origin activation checkpoint. EMBO J 29(19):3381–3394 · DOI
  34. Stebbing J, Paz K, Schwartz G, Wexler L, Maki R, Pollock R, Morris R, Cohen R, Shankar A, Blackman G, Harding V, Vasquez D, Krell J, Zacharoulis S, Ciznadija D, Katz A, Sidransky D (2014) Patient-derived xenografts for individualized care in advanced sarcoma. Cancer 120(13):2006–2015 · DOI
  35. Pessoa-Brandão L, Sclafani R (2004) CDC7/DBF4 functions in the translesion synthesis branch of the RAD6 epistasis group in Saccharomyces cerevisiae. Genetics 167(4):1597–1610 · DOI
  36. Sasi N, Bhutkar A, Lanning N, MacKeigan J, Weinreich M (2017) DDK promotes tumor chemoresistance and survival via multiple pathways. Neoplasia 19(5):439–450 · DOI
  37. Dubrez L (2017) Regulation of E2F1 transcription factor by ubiquitin conjugation. Int J Mol Sci 18(10). https://doi.org/10.3390/ijms18102188 · DOI

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Metadata

Authors
Jin, S., Ma, H., Yang, W., Ju, H., Wang, L., & Zhang, Z.
Affiliations
Shanghai Jiao Tong University (CN)
Corresponding author
Zhang, Zhiyuan
ORCID
Venue
Journal of Molecular Medicine
Publisher
Springer Science and Business Media LLC
Published
2018-04-30
Volume
96
Issue
6
Pages
513-525
ISSN
  • 0946-2716 (ISSN-L)
  • 1432-1440
DOI
10.1007/s00109-018-1636-7
OpenAlex
W2800264394
Cited by
18
References
1
Citations by year
2025: 4 · 2023: 2 · 2022: 3 · 2021: 4 · 2020: 1 · 2019: 3 · 2018: 1
FWCI
2.00
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Molecular Medicine (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (81430012)
  • Shanghai Jiao Tong University School of Medicine (BXJ201728)
Topics
  • Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Mechanisms and Therapy
Keywords
CDC7, oral squamous cell carcinoma, E2F1, DNA replication initiation, S phase, apoptosis, cisplatin, 5-fluorouracil, combination chemotherapy, cell proliferation, therapeutic target
MeSH terms
Animals, Antineoplastic Agents, Carcinoma, Squamous Cell, Cell Line, Cell Survival, Female, Humans, Male, Mice, Inbred BALB C, Mice, Nude, Middle Aged, Mouth Neoplasms, Pyrimidinones, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Cell Proliferation, E2F1 Transcription Factor

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