Tumor Biology

, Volume 36, Issue 11, pp 8325–8331 | Cite as

EBP1 suppresses growth, migration, and invasion of thyroid cancer cells through upregulating RASAL expression

  • Hongyan Liu
  • Zhenjie Li
  • Liujuan Li
  • Haiying Peng
  • Zhijun Zhang
Research Article


Ebp1, a protein identified by its interactions with the ErbB3 receptor, has been characterized as a negative regulator of cancers. RAS GTPase-activating protein (RasGAP), RASAL1, was recently identified as a major tumor suppressor in thyroid cancer. In this study, we examined EBP1 expression in papillary and follicular thyroid cancer cells. We found that compared with normal thyroid cells, TPC1, WRO, and FTC133 thyroid tumor cells exhibited lower EBP1 expression at messenger RNA (mRNA) and protein levels. We then investigated the effects of forced EBP1 expression on growth, migration, and invasiveness of thyroid tumor cells. By using MTT and Boyden chamber assays, we showed that EBP1 overexpression dramatically reduced growth rate, migration, and invasiveness of K1 and FTC133 thyroid tumor cells. Furthermore, we explored the molecular mechanism underlying the effects of EBP1 on the cells by disclosing the correlation of EBP1 and RASAL1 expression. RASAL expression was elevated in thyroid tumor cells overexpressing EBP1. Knockdown RASAL by transduction of RASAL1 shRNA lentiviral particles markedly reduced RASAL levels with restoration of EBP1, and RASAL1 knockdown abrogated the effects of forced EBP1 expression on cell growth, migration, and invasiveness of thyroid tumor cells. These findings suggest that Ebp1 suppressed thyroid cancer cell lines by upregulating RASRAL expression.


Thyroid cancer EBP1 RASAL1 Migration Invasiveness 


  1. 1.
    Jemal A, Bray F, Center M. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.CrossRefPubMedGoogle Scholar
  2. 2.
    Xing M. Molecular pathogenesis and mechanisms of thyroid cancer. Nat Rev Cancer. 2013;13(3):184–99.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Liu D, Yang C, Bojdani E, Murugan AK, Xing M. Identification of RASAL1 as a major tumor suppressor gene in thyroid cancer. J Natl Cancer Inst. 2013;105(21):1617–27.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Xing M. Gene methylation in thyroid tumorigenesis. Endocrinology. 2007;148(3):948–53.CrossRefPubMedGoogle Scholar
  5. 5.
    Hou P, Ji M, Xing M. Association of PTEN gene methylation with genetic alterations in the phosphatidylinositol 3-kinase/AKT signaling pathway in thyroid tumors. Cancer. 2008;113(9):2440–7.CrossRefPubMedGoogle Scholar
  6. 6.
    Alvarez-Nunez F, Bussaglia E, Mauricio D, Ybarra J, Vilar M, Lerma E, et al. PTEN promoter methylation in sporadic thyroid carcinomas. Thyroid. 2006;16(1):17–23.CrossRefPubMedGoogle Scholar
  7. 7.
    Radomski N, Jost E. Molecular cloning of a murine cDNA encoding a novel protein, p38-2G4, which varies with the cell cycle. Exp Cell Res. 1995;220:434–45.CrossRefPubMedGoogle Scholar
  8. 8.
    Sithanandam G, Anderson LM. The ERBB3 receptor in cancer and cancer gene therapy. Cancer Gene Ther. 2008;15:413–48.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Zhang Y, Fondell JD, Wang Q, Xia X, Cheng A, Lu ML, et al. Repression of androgen receptor mediated transcription by the ErbB-3 binding protein, Ebp1. Oncogene. 2002;21:5609–18.CrossRefPubMedGoogle Scholar
  10. 10.
    Zhang Y, Linn D, Liu Z, Melamed J, Tavora F, Young CY, et al. EBP1, an ErbB3-binding protein, is decreased in prostate cancer and implicated in hormone resistance. Mol Cancer Ther. 2008;7:3176–86.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Zhang Y, Wang XW, Jelovac D, Nakanishi T, Yu MH, Akinmade D, et al. The ErbB3-binding protein Ebp1 suppresses androgen receptor-mediated gene transcription and tumorigenesis of prostate cancer cells. Proc Natl Acad Sci U S A. 2005;102(28):9890–5.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Horak CE, Lee JH, Elkahloun AG, Boissan M, Dumont S, Maga TK, et al. Nm23-H1 suppresses tumor cell motility by down-regulating the lysophosphatidic acid receptor EDG2. Cancer Res. 2007;67:7238–46.CrossRefPubMedGoogle Scholar
  13. 13.
    Xu J, Wang R, Xie ZH, Odero-Marah V, Pathak S, Multani A, et al. Prostate cancer metastasis: role of the host microenvironment in promoting epithelial to mesenchymal transition and increased bone and adrenal gland metastasis. Prostate. 2006;66:1664–73.CrossRefPubMedGoogle Scholar
  14. 14.
    Rebollo A, Martinez A. Ras proteins: recent advances and new functions. Blood. 1999;94(9):2971–80.PubMedGoogle Scholar
  15. 15.
    Vigil D, Cherfils J, Rossman KL, Der CJ. Ras superfamily GEFs and GAPs: validated and tractable targets for cancer therapy? Nat Rev Cancer. 2010;10(12):842–57.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Hongyan Liu
    • 1
  • Zhenjie Li
    • 1
  • Liujuan Li
    • 1
  • Haiying Peng
    • 2
  • Zhijun Zhang
    • 3
  1. 1.Department of EndocrinologyLinyi People’s HospitalLinyiChina
  2. 2.Department of Clinical Laboratory MedicineLinyi People’s HospitalLinyiChina
  3. 3.Department of SurgeryPeople’s Hospital of Linzi District Affiliated to Binzhou Medical CollegeZiboChina

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