Potential significance of EMP3 in patients with upper urinary tract urothelial carcinoma: Crosstalk with ErbB2-PI3K-Akt pathway

Yi Wen Wang, Wei Ming Li, Wen Jeng Wu, Chee Yin Chai, Hsiao-Sheng Liu, Ming Derg Lai, Nan Haw Chow

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Purpose Upper urinary tract (pyelocalyceal cavities and ureter) urothelial carcinoma is a relatively rare neoplastic disease. Although diagnosis and treatment of this tumor variant have improved significantly, accurate risk stratification remains a challenge. To identify the putative oncogene involved in urothelial carcinoma progression we performed bioinformatics guided experimental investigation targeting chromosome 19q13. Materials and Methods We investigated the effects of EMP3 on cancer cell growth, migration and adhesion in transfection and siRNA experiments in vitro. Crosstalk of integrins or ErbB2 with EMP3 was examined by reverse transcriptase-polymerase chain reaction and immunoblot. The potential involvement of epigenetic alterations of EMP3 in vitro and in vivo was analyzed by methylation specific polymerase chain reaction. To validate clinical relevance we measured EMP3 expression at the mRNA and protein levels in a cohort of 77 patients with upper urinary tract urothelial carcinoma and compared prognostic significance in relation to that of ErbB2 expression. Results We noted functional crosstalk between ErbB2 and EMP3 in vitro. EMP3 over expression promoted cancer cell proliferation and migration but suppressed cell adhesion in vitro. EMP3 activated the ErbB2-PI3K-AKT pathway to increase cell growth in vitro. In the clinical cohort Kaplan-Meier survival estimates showed that ErbB2 and EMP3 co-expression was the most important indicator of progression-free and metastasis-free survival in patients with upper urinary tract urothelial carcinoma (log rank test p = 0.018 and 0.04, respectively). Conclusions EMP3 is an important prognostic indicator for selecting patients with upper urinary tract urothelial carcinoma for more intensive therapy. EMP3 is an innovative co-targeting candidate for designing ErbB2 based cancer therapy.

Original languageEnglish
Pages (from-to)242-251
Number of pages10
JournalJournal of Urology
Volume192
Issue number1
DOIs
Publication statusPublished - 2014 Jan 1

Fingerprint

Urinary Tract
Phosphatidylinositol 3-Kinases
Carcinoma
Cell Adhesion
Cell Movement
Neoplasms
Survival
Kaplan-Meier Estimate
Ureter
Growth
Rare Diseases
Computational Biology
Reverse Transcriptase Polymerase Chain Reaction
Oncogenes
Epigenomics
Integrins
Methylation
Small Interfering RNA
Transfection
Therapeutics

All Science Journal Classification (ASJC) codes

  • Urology

Cite this

@article{4e302e8480aa4c64bc242742064650e6,
title = "Potential significance of EMP3 in patients with upper urinary tract urothelial carcinoma: Crosstalk with ErbB2-PI3K-Akt pathway",
abstract = "Purpose Upper urinary tract (pyelocalyceal cavities and ureter) urothelial carcinoma is a relatively rare neoplastic disease. Although diagnosis and treatment of this tumor variant have improved significantly, accurate risk stratification remains a challenge. To identify the putative oncogene involved in urothelial carcinoma progression we performed bioinformatics guided experimental investigation targeting chromosome 19q13. Materials and Methods We investigated the effects of EMP3 on cancer cell growth, migration and adhesion in transfection and siRNA experiments in vitro. Crosstalk of integrins or ErbB2 with EMP3 was examined by reverse transcriptase-polymerase chain reaction and immunoblot. The potential involvement of epigenetic alterations of EMP3 in vitro and in vivo was analyzed by methylation specific polymerase chain reaction. To validate clinical relevance we measured EMP3 expression at the mRNA and protein levels in a cohort of 77 patients with upper urinary tract urothelial carcinoma and compared prognostic significance in relation to that of ErbB2 expression. Results We noted functional crosstalk between ErbB2 and EMP3 in vitro. EMP3 over expression promoted cancer cell proliferation and migration but suppressed cell adhesion in vitro. EMP3 activated the ErbB2-PI3K-AKT pathway to increase cell growth in vitro. In the clinical cohort Kaplan-Meier survival estimates showed that ErbB2 and EMP3 co-expression was the most important indicator of progression-free and metastasis-free survival in patients with upper urinary tract urothelial carcinoma (log rank test p = 0.018 and 0.04, respectively). Conclusions EMP3 is an important prognostic indicator for selecting patients with upper urinary tract urothelial carcinoma for more intensive therapy. EMP3 is an innovative co-targeting candidate for designing ErbB2 based cancer therapy.",
author = "Wang, {Yi Wen} and Li, {Wei Ming} and Wu, {Wen Jeng} and Chai, {Chee Yin} and Hsiao-Sheng Liu and Lai, {Ming Derg} and Chow, {Nan Haw}",
year = "2014",
month = "1",
day = "1",
doi = "10.1016/j.juro.2013.12.001",
language = "English",
volume = "192",
pages = "242--251",
journal = "Journal of Urology",
issn = "0022-5347",
publisher = "Elsevier Inc.",
number = "1",

}

Potential significance of EMP3 in patients with upper urinary tract urothelial carcinoma : Crosstalk with ErbB2-PI3K-Akt pathway. / Wang, Yi Wen; Li, Wei Ming; Wu, Wen Jeng; Chai, Chee Yin; Liu, Hsiao-Sheng; Lai, Ming Derg; Chow, Nan Haw.

In: Journal of Urology, Vol. 192, No. 1, 01.01.2014, p. 242-251.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Potential significance of EMP3 in patients with upper urinary tract urothelial carcinoma

T2 - Crosstalk with ErbB2-PI3K-Akt pathway

AU - Wang, Yi Wen

AU - Li, Wei Ming

AU - Wu, Wen Jeng

AU - Chai, Chee Yin

AU - Liu, Hsiao-Sheng

AU - Lai, Ming Derg

AU - Chow, Nan Haw

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Purpose Upper urinary tract (pyelocalyceal cavities and ureter) urothelial carcinoma is a relatively rare neoplastic disease. Although diagnosis and treatment of this tumor variant have improved significantly, accurate risk stratification remains a challenge. To identify the putative oncogene involved in urothelial carcinoma progression we performed bioinformatics guided experimental investigation targeting chromosome 19q13. Materials and Methods We investigated the effects of EMP3 on cancer cell growth, migration and adhesion in transfection and siRNA experiments in vitro. Crosstalk of integrins or ErbB2 with EMP3 was examined by reverse transcriptase-polymerase chain reaction and immunoblot. The potential involvement of epigenetic alterations of EMP3 in vitro and in vivo was analyzed by methylation specific polymerase chain reaction. To validate clinical relevance we measured EMP3 expression at the mRNA and protein levels in a cohort of 77 patients with upper urinary tract urothelial carcinoma and compared prognostic significance in relation to that of ErbB2 expression. Results We noted functional crosstalk between ErbB2 and EMP3 in vitro. EMP3 over expression promoted cancer cell proliferation and migration but suppressed cell adhesion in vitro. EMP3 activated the ErbB2-PI3K-AKT pathway to increase cell growth in vitro. In the clinical cohort Kaplan-Meier survival estimates showed that ErbB2 and EMP3 co-expression was the most important indicator of progression-free and metastasis-free survival in patients with upper urinary tract urothelial carcinoma (log rank test p = 0.018 and 0.04, respectively). Conclusions EMP3 is an important prognostic indicator for selecting patients with upper urinary tract urothelial carcinoma for more intensive therapy. EMP3 is an innovative co-targeting candidate for designing ErbB2 based cancer therapy.

AB - Purpose Upper urinary tract (pyelocalyceal cavities and ureter) urothelial carcinoma is a relatively rare neoplastic disease. Although diagnosis and treatment of this tumor variant have improved significantly, accurate risk stratification remains a challenge. To identify the putative oncogene involved in urothelial carcinoma progression we performed bioinformatics guided experimental investigation targeting chromosome 19q13. Materials and Methods We investigated the effects of EMP3 on cancer cell growth, migration and adhesion in transfection and siRNA experiments in vitro. Crosstalk of integrins or ErbB2 with EMP3 was examined by reverse transcriptase-polymerase chain reaction and immunoblot. The potential involvement of epigenetic alterations of EMP3 in vitro and in vivo was analyzed by methylation specific polymerase chain reaction. To validate clinical relevance we measured EMP3 expression at the mRNA and protein levels in a cohort of 77 patients with upper urinary tract urothelial carcinoma and compared prognostic significance in relation to that of ErbB2 expression. Results We noted functional crosstalk between ErbB2 and EMP3 in vitro. EMP3 over expression promoted cancer cell proliferation and migration but suppressed cell adhesion in vitro. EMP3 activated the ErbB2-PI3K-AKT pathway to increase cell growth in vitro. In the clinical cohort Kaplan-Meier survival estimates showed that ErbB2 and EMP3 co-expression was the most important indicator of progression-free and metastasis-free survival in patients with upper urinary tract urothelial carcinoma (log rank test p = 0.018 and 0.04, respectively). Conclusions EMP3 is an important prognostic indicator for selecting patients with upper urinary tract urothelial carcinoma for more intensive therapy. EMP3 is an innovative co-targeting candidate for designing ErbB2 based cancer therapy.

UR - http://www.scopus.com/inward/record.url?scp=84902544160&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84902544160&partnerID=8YFLogxK

U2 - 10.1016/j.juro.2013.12.001

DO - 10.1016/j.juro.2013.12.001

M3 - Article

C2 - 24333112

AN - SCOPUS:84902544160

VL - 192

SP - 242

EP - 251

JO - Journal of Urology

JF - Journal of Urology

SN - 0022-5347

IS - 1

ER -