High Expression of HEF1 is Associated with Poor Prognosis in Urinary Bladder Carcinoma

Overview

Journal Onco Targets Ther

Publisher Dove Medical Press

Specialty Oncology

Date 2014 Aug 6

PMID 25092988

Citations 7

Authors

Qi Zhang

Hui-Ju Wang

Da-Hong Zhang

Guo-Qing Ru

Xu-Jun He

Ying-Yu Ma

Affiliations

Soon will be listed here.

Abstract

Human enhancer of filamentation 1 (HEF1) is a multidomain scaffolding protein that has been thought to play an important role in the tumor progression of various cancers. HEF1 expression has not previously been reported in urinary bladder carcinoma, and little is known about its prognostic significance. The aim of this study was to evaluate the expression patterns of HEF1 in urinary bladder carcinoma and to investigate its prognostic significance. HEF1 expression was analyzed by immunohistochemistry using tissue microarray. A significant relationship between HEF1 expression and sex, tumor size, number of tumors, invasion depth, lymph node metastasis, and distant metastasis was found, and high expression of HEF1 was associated with worse overall survival when compared to low expression of HEF1. Multivariate analysis showed that HEF1 expression was an independent prognostic factor for overall survival in urinary bladder carcinoma. We investigated HEF1 expression in urinary bladder carcinoma and found that high HEF1 expression was associated with advanced stage, large tumor size, and shortened progression-free survival. Although the biologic function of HEF1 in urinary bladder carcinoma remains unknown, the expression of HEF1 can provide new prognostic information for disease progression.

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References

Xia D, Holla V, Wang D, Menter D, DuBois R . HEF1 is a crucial mediator of the proliferative effects of prostaglandin E(2) on colon cancer cells. Cancer Res. 2010; 70(2):824-31. PMC: 2943830. DOI: 10.1158/0008-5472.CAN-09-2105. View

Li Y, Bavarva J, Wang Z, Guo J, Qian C, Thibodeau S . HEF1, a novel target of Wnt signaling, promotes colonic cell migration and cancer progression. Oncogene. 2011; 30(23):2633-43. PMC: 3164309. DOI: 10.1038/onc.2010.632. View

Tikhmyanova N, Golemis E . NEDD9 and BCAR1 negatively regulate E-cadherin membrane localization, and promote E-cadherin degradation. PLoS One. 2011; 6(7):e22102. PMC: 3134485. DOI: 10.1371/journal.pone.0022102. View

Zhang Q, Ye Z, Yang Q, He X, Wang H, Zhao Z . Upregulated expression of annexin II is a prognostic marker for patients with gastric cancer. World J Surg Oncol. 2012; 10:103. PMC: 3433344. DOI: 10.1186/1477-7819-10-103. View

Lee R, Droller M . The natural history of bladder cancer. Implications for therapy. Urol Clin North Am. 2000; 27(1):1-13, vii. DOI: 10.1016/s0094-0143(05)70229-9. View

ONeill G, Fashena S, Golemis E . Integrin signalling: a new Cas(t) of characters enters the stage. Trends Cell Biol. 2000; 10(3):111-9. DOI: 10.1016/s0962-8924(99)01714-6. View

Kim S, Xia D, Kim S, Holla V, Menter D, DuBois R . Human enhancer of filamentation 1 Is a mediator of hypoxia-inducible factor-1alpha-mediated migration in colorectal carcinoma cells. Cancer Res. 2010; 70(10):4054-63. PMC: 2871069. DOI: 10.1158/0008-5472.CAN-09-2110. View

Izumchenko E, Singh M, Plotnikova O, Tikhmyanova N, Little J, Serebriiskii I . NEDD9 promotes oncogenic signaling in mammary tumor development. Cancer Res. 2009; 69(18):7198-206. PMC: 2758619. DOI: 10.1158/0008-5472.CAN-09-0795. View

Pugacheva E, Golemis E . The focal adhesion scaffolding protein HEF1 regulates activation of the Aurora-A and Nek2 kinases at the centrosome. Nat Cell Biol. 2005; 7(10):937-46. PMC: 2652766. DOI: 10.1038/ncb1309. View

10.

Singh M, Izumchenko E, Klein-Szanto A, Egleston B, Wolfson M, Golemis E . Enhanced genetic instability and dasatinib sensitivity in mammary tumor cells lacking NEDD9. Cancer Res. 2010; 70(21):8907-16. PMC: 2970659. DOI: 10.1158/0008-5472.CAN-10-0353. View

11.

Kim M, Gans J, Nogueira C, Wang A, Paik J, Feng B . Comparative oncogenomics identifies NEDD9 as a melanoma metastasis gene. Cell. 2006; 125(7):1269-81. DOI: 10.1016/j.cell.2006.06.008. View

12.

Bradbury P, Mahmassani M, Zhong J, Turner K, Paul A, Verrills N . PP2A phosphatase suppresses function of the mesenchymal invasion regulator NEDD9. Biochim Biophys Acta. 2011; 1823(2):290-7. DOI: 10.1016/j.bbamcr.2011.10.011. View

13.

ONeill G, Seo S, Serebriiskii I, Lessin S, Golemis E . A new central scaffold for metastasis: parsing HEF1/Cas-L/NEDD9. Cancer Res. 2007; 67(19):8975-9. PMC: 2637184. DOI: 10.1158/0008-5472.CAN-07-1328. View

14.

Chang J, Gao F, Zhao G, Zhang G . Expression and clinical significance of NEDD9 in lung tissues. Med Oncol. 2012; 29(4):2654-60. DOI: 10.1007/s12032-012-0213-0. View

15.

Natarajan M, Stewart J, Golemis E, Pugacheva E, Alexandropoulos K, Cox B . HEF1 is a necessary and specific downstream effector of FAK that promotes the migration of glioblastoma cells. Oncogene. 2005; 25(12):1721-32. DOI: 10.1038/sj.onc.1209199. View

16.

Kong C, Wang C, Wang L, Ma M, Niu C, Sun X . NEDD9 is a positive regulator of epithelial-mesenchymal transition and promotes invasion in aggressive breast cancer. PLoS One. 2011; 6(7):e22666. PMC: 3145662. DOI: 10.1371/journal.pone.0022666. View

17.

Law S, Zhang Y, Klein-Szanto A, Golemis E . Cell cycle-regulated processing of HEF1 to multiple protein forms differentially targeted to multiple subcellular compartments. Mol Cell Biol. 1998; 18(6):3540-51. PMC: 108935. DOI: 10.1128/MCB.18.6.3540. View

18.

Singh M, Cowell L, Seo S, ONeill G, Golemis E . Molecular basis for HEF1/NEDD9/Cas-L action as a multifunctional co-ordinator of invasion, apoptosis and cell cycle. Cell Biochem Biophys. 2007; 48(1):54-72. PMC: 1976382. DOI: 10.1007/s12013-007-0036-3. View

19.

Scrimger R, Murtha A, Parliament M, Venner P, Hanson J, Houle G . Muscle-invasive transitional cell carcinoma of the urinary bladder: a population-based study of patterns of care and prognostic factors. Int J Radiat Oncol Biol Phys. 2001; 51(1):23-30. DOI: 10.1016/s0360-3016(01)01591-7. View

20.

Vieweg J, Gschwend J, Herr H, Fair W . Pelvic lymph node dissection can be curative in patients with node positive bladder cancer. J Urol. 1999; 161(2):449-54. View