Human epididymis protein 4 (HE4) plays a key role in ovarian cancer cell adhesion and motility

Renquan Lu, Xinghui Sun, Ran Xiao, Lei Zhou, Xiang Gao, Lin Guo

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Human epididymis protein 4 (HE4) is a novel and specific biomarker for epithelial ovarian cancer (EOC). We previously demonstrated that serum HE4 levels were significantly elevated in the majority of EOC patients but not in subjects with benign disease or healthy controls. However, the precise mechanism of HE4 protein function is unknown. In this study, we generated HE4-overexpressing SKOV3 cells and found that stably transduced cells promoted cell adhesion and migration. Knockdown of HE4 expression was achieved by stable transfection of SKOV3 cells with a construct encoding a short hairpin DNA directed against the HE4 gene. Correspondingly, the proliferation and spreading ability of HE4-expressed cells were inhibited by HE4 suppression. Mechanistically, impaired EGFR and Erk1/2 phosphorylation were observed in cells with HE4 knockdown. The phosphorylation was restored when the knockdown cells were cultured in conditioned medium containing HE4. Moreover, . in vivo tumorigenicity showed that HE4 suppression markedly inhibited the growth of tumors. This suggests that expression of HE4 is associated with cancer cell adhesion, migration and tumor growth, which can be related to its effects on the EGFR-MAPK signaling pathway. Our results provide evidence of the cellular and molecular mechanisms that may underlie the motility-promoting role of HE4 in EOC progression. The role of HE4 as a target for gene-based therapy might be considered in future studies.

Original languageEnglish (US)
Pages (from-to)274-280
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume419
Issue number2
DOIs
StatePublished - Mar 9 2012

Fingerprint

Epididymis
Cell adhesion
Cell Adhesion
Ovarian Neoplasms
Cell Movement
Proteins
Phosphorylation
Tumors
Genes
Neoplasms
Biomarkers
Conditioned Culture Medium
Growth
Genetic Therapy
Transfection

Keywords

  • Human epididymis protein 4
  • MAPK signaling pathway
  • Ovarian neoplasm
  • RNA interference

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Human epididymis protein 4 (HE4) plays a key role in ovarian cancer cell adhesion and motility. / Lu, Renquan; Sun, Xinghui; Xiao, Ran; Zhou, Lei; Gao, Xiang; Guo, Lin.

In: Biochemical and Biophysical Research Communications, Vol. 419, No. 2, 09.03.2012, p. 274-280.

Research output: Contribution to journalArticle

Lu, Renquan ; Sun, Xinghui ; Xiao, Ran ; Zhou, Lei ; Gao, Xiang ; Guo, Lin. / Human epididymis protein 4 (HE4) plays a key role in ovarian cancer cell adhesion and motility. In: Biochemical and Biophysical Research Communications. 2012 ; Vol. 419, No. 2. pp. 274-280.
@article{f1adbd399dc74801a6af2bddd36b4285,
title = "Human epididymis protein 4 (HE4) plays a key role in ovarian cancer cell adhesion and motility",
abstract = "Human epididymis protein 4 (HE4) is a novel and specific biomarker for epithelial ovarian cancer (EOC). We previously demonstrated that serum HE4 levels were significantly elevated in the majority of EOC patients but not in subjects with benign disease or healthy controls. However, the precise mechanism of HE4 protein function is unknown. In this study, we generated HE4-overexpressing SKOV3 cells and found that stably transduced cells promoted cell adhesion and migration. Knockdown of HE4 expression was achieved by stable transfection of SKOV3 cells with a construct encoding a short hairpin DNA directed against the HE4 gene. Correspondingly, the proliferation and spreading ability of HE4-expressed cells were inhibited by HE4 suppression. Mechanistically, impaired EGFR and Erk1/2 phosphorylation were observed in cells with HE4 knockdown. The phosphorylation was restored when the knockdown cells were cultured in conditioned medium containing HE4. Moreover, . in vivo tumorigenicity showed that HE4 suppression markedly inhibited the growth of tumors. This suggests that expression of HE4 is associated with cancer cell adhesion, migration and tumor growth, which can be related to its effects on the EGFR-MAPK signaling pathway. Our results provide evidence of the cellular and molecular mechanisms that may underlie the motility-promoting role of HE4 in EOC progression. The role of HE4 as a target for gene-based therapy might be considered in future studies.",
keywords = "Human epididymis protein 4, MAPK signaling pathway, Ovarian neoplasm, RNA interference",
author = "Renquan Lu and Xinghui Sun and Ran Xiao and Lei Zhou and Xiang Gao and Lin Guo",
year = "2012",
month = "3",
day = "9",
doi = "10.1016/j.bbrc.2012.02.008",
language = "English (US)",
volume = "419",
pages = "274--280",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Human epididymis protein 4 (HE4) plays a key role in ovarian cancer cell adhesion and motility

AU - Lu, Renquan

AU - Sun, Xinghui

AU - Xiao, Ran

AU - Zhou, Lei

AU - Gao, Xiang

AU - Guo, Lin

PY - 2012/3/9

Y1 - 2012/3/9

N2 - Human epididymis protein 4 (HE4) is a novel and specific biomarker for epithelial ovarian cancer (EOC). We previously demonstrated that serum HE4 levels were significantly elevated in the majority of EOC patients but not in subjects with benign disease or healthy controls. However, the precise mechanism of HE4 protein function is unknown. In this study, we generated HE4-overexpressing SKOV3 cells and found that stably transduced cells promoted cell adhesion and migration. Knockdown of HE4 expression was achieved by stable transfection of SKOV3 cells with a construct encoding a short hairpin DNA directed against the HE4 gene. Correspondingly, the proliferation and spreading ability of HE4-expressed cells were inhibited by HE4 suppression. Mechanistically, impaired EGFR and Erk1/2 phosphorylation were observed in cells with HE4 knockdown. The phosphorylation was restored when the knockdown cells were cultured in conditioned medium containing HE4. Moreover, . in vivo tumorigenicity showed that HE4 suppression markedly inhibited the growth of tumors. This suggests that expression of HE4 is associated with cancer cell adhesion, migration and tumor growth, which can be related to its effects on the EGFR-MAPK signaling pathway. Our results provide evidence of the cellular and molecular mechanisms that may underlie the motility-promoting role of HE4 in EOC progression. The role of HE4 as a target for gene-based therapy might be considered in future studies.

AB - Human epididymis protein 4 (HE4) is a novel and specific biomarker for epithelial ovarian cancer (EOC). We previously demonstrated that serum HE4 levels were significantly elevated in the majority of EOC patients but not in subjects with benign disease or healthy controls. However, the precise mechanism of HE4 protein function is unknown. In this study, we generated HE4-overexpressing SKOV3 cells and found that stably transduced cells promoted cell adhesion and migration. Knockdown of HE4 expression was achieved by stable transfection of SKOV3 cells with a construct encoding a short hairpin DNA directed against the HE4 gene. Correspondingly, the proliferation and spreading ability of HE4-expressed cells were inhibited by HE4 suppression. Mechanistically, impaired EGFR and Erk1/2 phosphorylation were observed in cells with HE4 knockdown. The phosphorylation was restored when the knockdown cells were cultured in conditioned medium containing HE4. Moreover, . in vivo tumorigenicity showed that HE4 suppression markedly inhibited the growth of tumors. This suggests that expression of HE4 is associated with cancer cell adhesion, migration and tumor growth, which can be related to its effects on the EGFR-MAPK signaling pathway. Our results provide evidence of the cellular and molecular mechanisms that may underlie the motility-promoting role of HE4 in EOC progression. The role of HE4 as a target for gene-based therapy might be considered in future studies.

KW - Human epididymis protein 4

KW - MAPK signaling pathway

KW - Ovarian neoplasm

KW - RNA interference

UR - http://www.scopus.com/inward/record.url?scp=84862809311&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862809311&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2012.02.008

DO - 10.1016/j.bbrc.2012.02.008

M3 - Article

VL - 419

SP - 274

EP - 280

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 2

ER -