Skip to main content

Advertisement

SpringerLink
Log in

Notch2 signaling contributes to cell growth, invasion, and migration in salivary adenoid cystic carcinoma

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

Abstract

Many studies have explored whether the Notch signaling pathway has a tumor-suppressive or an oncogenic role in various tumors; however, the role of the Notch signaling pathway in salivary adenoid cystic carcinoma (SACC) is still unknown. In this study, we attempt to define the role of Notch2 signaling in cell growth, invasion, and migration in SACC. We compared Notch2 expression in clinical SACC samples with that of normal samples by using immunohistochemical staining. Then, we down-regulated Notch2 expression to observe the effect of Notch2 on proliferation, invasion, migration, and the expression of known target genes of Notch signal pathway. According to our results, Notch2 expression was higher in SACC tissues compared with normal tissues. Knockdown of Notch2 inhibited cell proliferation, invasion, and migration in vitro and down-regulated the expression of HEY2 and CCND1. The results of this study suggest that Notch2 has an essential role in the cell growth, invasion, and migration of SACC. Notch2 may therefore be a potential target gene for the treatment of SACC by interfering with cell growth and metastasis.

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
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Liu J, Shao C, Tan ML, Mu D, Ferris RL, Ha PK (2012) Molecular biology of adenoid cystic carcinoma. Head Neck 34:1665–1677

    Article  PubMed Central  PubMed  Google Scholar 

  2. Zhang CY, Zhao YX, Xia RH, Han J, Wang BS, Tian Z, Wang LZ, Hu YH, Li J (2014) RASSF1A promoter hypermethylation is a strong biomarker of poor survival in patients with salivary adenoid cystic carcinoma in a Chinese population. PLoS ONE 9:e110159

    Article  PubMed Central  PubMed  Google Scholar 

  3. Bell D, Bell A, Roberts D, Weber RS, El-Naggar AK (2012) Developmental transcripti-on factor EN1—a novel biomarker in human salivary gland adenoid cystic carcinoma. Cancer 118:1282–1292

    Article  Google Scholar 

  4. Liu X, Zhang Y, Ren W, Rao G (2010) ErbB2 gene silencing and its effect on PTEN in SACC-83 salivary adenoid cystic carcinoma cells. Oncol Rep 24:1291–1296

    CAS  PubMed  Google Scholar 

  5. Laurie SA, Ho AL, Fury MG, Sherman E, Pfister DG (2011) Systemic therapy in the management of metastatic or locally recurrent adenoid cystic carcinoma of the salivary glands: a systematic review. Lancet Oncol 12:815–824

    Article  CAS  PubMed  Google Scholar 

  6. Mohr OL (1919) Character changed caused by mutation of an entire region of a chromosome in Drosophila. Genetics 4:275–282

    PubMed Central  CAS  PubMed  Google Scholar 

  7. Lu J, Ye X, Fan F, Xia L, Bhattacharya R, Bellister S, Tozzi F, Sceusi E, Zhou Y, Tachibana I, Maru DM, Hawke DH, Rak J, Mani SA, Zweidler-McKay P, Ellis LM (2013) Endothelial cells promote the colorectal cancer stem cell phenotype through a soluble form of Jagged-1. Cancer Cell 23:171–185

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Bailey AM, Posakony JW (1995) Suppressor of hairless directly activates transcription of enhancer of split complex genes in response to Notch receptor activity. Genes Rev 9:2609–2622

    Article  CAS  Google Scholar 

  9. Jarriault S, Le Bail O, Hirsinger E, Pourquié O, Logeat F, Strong CF, Brou C, Seidah NG, Isra IA (1998) Delta-1 activation of notch-1 signaling results in HES-1 transactivation. Mol Cell Biol 18:7423–7431

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Su BH, Qu J, Song M, Huang XY, Hu XM, Xie J, Zhao Y, Ding LC, She L, Chen J, Lin LS, Lin X, Zheng DL, Lu YG (2014) NOTCH1 signaling contributes to cell growth, anti-apoptosis and metastasis in salivary adenoid cystic carcinoma. Oncotarget 16:6885–6895

    Article  Google Scholar 

  11. Groeneweg JW, Foster R, Growdon WB, Verheijen R, Rueda BR (2014) Notch signaling in serous ovarian cancer. J Ovarian Res 7:95

    Article  PubMed Central  PubMed  Google Scholar 

  12. Iso T, Kedes L, Hamamori Y (2003) HES and HERP families: multiple effectors of the Notch signaling pathway. J Cell Physiol 194:237–255

    Article  CAS  PubMed  Google Scholar 

  13. Maier MM, Gessler M (2000) Comparative analysis of the human and mouse Hey1 promoter: Hey genes are new Notch target genes. Biochem Biophys Res Commun 275:652–660

    Article  CAS  PubMed  Google Scholar 

  14. Lu YG, Zhou HY, Ding LC, Mei Y, Xiong RH, Deng SS, Yang HJ (2006) Analysis of differential expression genes related to different metastasis potential of adenoid cystic carcinoma using restriction fragments differential display PCR. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 23:505–510

    CAS  PubMed  Google Scholar 

  15. Ding LC, She L, Zheng DL, Huang QL, Wang JF, Zheng FF, Lu YG (2010) Notch-4 contributes to the metastasis of salivary adenoid cystic carcinoma. Oncol Rep 24:363–368

    CAS  PubMed  Google Scholar 

  16. Brzozowa M, Mielańczyk L, Michalski M, Malinowski L, Kowalczyk-Ziomek G, Helewski K, Harabin-Słowińska M, Wojnicz R (2013) Role of Notch signaling pathway in gastric cancer pathogenesis. Contemp Oncol (Pozn) 17:1–5

    CAS  Google Scholar 

  17. Ellisen LW, Bird J, West DC, Soreng AL, Reynolds TC, Smith SD, Sklar J (1991) TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. Cell 66:649–661

    Article  CAS  PubMed  Google Scholar 

  18. Stylianou S, Clarke RB, Brennan K (2006) Aberrant activation of notch signaling in human breast cancer. Cancer Res 66:1517–1525

    Article  CAS  PubMed  Google Scholar 

  19. Flores AN, McDermott N, Meunier A, Marignol L (2014) NUMB inhibition of NOTCH signalling as a therapeutic target in prostate cancer. Nat Rev Urol 11:499–507

    Article  CAS  PubMed  Google Scholar 

  20. Purow B (2012) Notch inhibition as a promising new approach to cancer therapy. Adv Exp Med Biol 727:305–319

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Fan X, Khaki L, Zhu TS, Soules ME, Talsma CE, Gul N, Koh C, Zhang J, Li YM, Maciaczyk J, Nikkhah G, Dimeco F, Piccirillo S, Vescovi AL, Eberhart CG (2010) NOTCH pathway blockade depletes CD133-positive glioblastoma cells and inhibits growth of tumor neurospheres and xenografts. Stem Cells 28:5–16

    PubMed Central  CAS  PubMed  Google Scholar 

  22. Sikandar SS, Pate KT, Anderson S, Dizon D, Edwards RA, Waterman ML, Lipkin SM (2010) NOTCH signaling is required for formation and self-renewal of tumor-initiating cells and for repression of secretory cell differentiation in colon cancer. Cancer Res 70:1469–1478

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Fu YP, Edvardsen H, Kaushiva A, Arhancet JP, Howe TM, Kohaar I, Porter-Gill P, Shah A, Landmark-Hoyvik H, Fossa SD, Ambs S, Naume B, Borresen-Dale AL, Kristensen VN, Prokunina-Olsson L (2010) NOTCH2 in breast cancer: association of SNP rs11249433 with gene expression in ER-positive breast tumors without TP53 mutations. Mol Cancer 9:113

    Article  PubMed Central  PubMed  Google Scholar 

  24. Chu D, Zheng J, Wang W, Zhao Q, Li Y, Li J, Xie H, Zhang H, Dong G, Xu C, Li M, Chen D, Ji G (2009) Notch2 expression is decreased in colorectal cancer and related to tumor differentiation status. Ann Surg Oncol 16:3259–3266

    Article  PubMed  Google Scholar 

  25. Chu D, Zhang Z, Zhou Y, Wang W, Li Y, Zhang H, Dong G, Zhao Q, Ji G (2011) Notch1 and Notch2 have opposite prognostic effects on patients with colorectal cancer. Ann Oncol 22:2440–2447

    Article  CAS  PubMed  Google Scholar 

  26. Hubmann R, Schwarzmeier JD, Shehata M, Hilgarth M, Duechler M, Dettke M, Berger R (2002) Notch2 is involved in the overexpression of CD23 in B-cell chronic lymphocytic leukemia. Blood 99:3742–3747

    Article  CAS  PubMed  Google Scholar 

  27. Fan X, Mikolaenko I, Elhassan I, Ni X, Wang Y, Ball D, Brat DJ, Perry A, Eberhart CG (2004) Notch1 and notch2 have opposite effects on embryonal brain tumor growth. Cancer Res 6:7787–7793

    Article  Google Scholar 

  28. Zhou L, Zhang N, Song W, You N, Li Q, Sun W, Zhang Y, Wang D, Dou K (2013) The significance of Notch1 compared with Notch3 in high metastasis and poor overall survival in hepatocellular carcinoma. PLoS ONE 8:e57382

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Luo DH, Zhou Q, Hu SK, Xia YQ, Xu CC, Lin TS, Pan YT, Wu JS, Jin R (2014) Differential expression of Notch1 intracellular domain and p21 proteins, and their clinical significance in gastric cancer. Oncol Lett 7:471–478

    PubMed Central  PubMed  Google Scholar 

  30. Li Y, Takeshita K, Liu PY, Satoh M, Oyama N, Mukai Y, Chin MT, Krebs L, Kotlikoff MI, Radtke F, Gridley T, Liao JK (2009) Smooth muscle Notch1 mediates neointimal formation after vascular injury. Circulation 119:2686–2692

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Musgrove EA, Caldon CE, Barraclough J, Stone A, Sutherland RL (2011) Cyclin D as a therapeutic target in cancer. Nat Rev Cancer 11:558–572

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Natural Sciences Foundation of China (No. 81172583), the Natural Sciences Foundation of Fujian (project numbers 2011J01167), and the Key Project of Science and Technology Foundation of Fujian Province of China (No. 2011Y0025) and Fujian Medical Innovation Grant (2014-CX-26).

Author information

Authors and Affiliations

  1. Department of Preventive Dentistry, Affiliated Stomatological Hospital, Fujian Medical University, Fuzhou, 350002, Fujian, People’s Republic of China

    Jing Qu, Min Song, Jian Xie, Xiao-Yu Huang, Xiao-Meng Hu, Rui-Huan Gan & You-Guang Lu

  2. Department of Pathology, Affiliated Stomatological Hospital, Fujian Medical University, Fuzhou, 350002, Fujian, People’s Republic of China

    Yong Zhao

  3. Department of Oral and Maxillofacial Surgery, Affiliated First Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, People’s Republic of China

    Li-Song Lin

  4. Center of Dental Implant, Affiliated Stomatological Hospital, Fujian Medical University, Fuzhou, 350002, Fujian, People’s Republic of China

    Jiang Chen

  5. Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, 350108, People’s Republic of China

    Xu Lin & Da-Li Zheng

Authors
  1. Jing Qu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Min Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jian Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiao-Yu Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiao-Meng Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rui-Huan Gan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yong Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Li-Song Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jiang Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Xu Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Da-Li Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. You-Guang Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Da-Li Zheng or You-Guang Lu.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (doc 43 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Qu, J., Song, M., Xie, J. et al. Notch2 signaling contributes to cell growth, invasion, and migration in salivary adenoid cystic carcinoma. Mol Cell Biochem 411, 135–141 (2016). https://doi.org/10.1007/s11010-015-2575-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-015-2575-z

Keywords

Search

Navigation