Effect of WFDC 2 silencing on the proliferation, motility and invasion of human serous ovarian cancer cells in vitro

Zhu, Yafei; Gao, Gan; Tang, Sheng-Bo; Zhang, Zhendong; Huang, Qingshui

doi:10.1016/s1995-7645(13)60055-3

Cited by 30 publications

(39 citation statements)

References 13 publications

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“…Using endometrial cancer cell lines and mouse ectopic subcutaneous cancer models, this and other groups have shown that overexpression of HE4 led to increased cell proliferation and faster cancer progression. In ovarian cancer and EC, HE4 was found to promote cancer cell growth in vitro (30)(31)(32). HE4-induced anti-apoptosis and drug resistance in ovarian cancer cell lines have also been reported (33,34).…”

Section: Introductionmentioning

confidence: 89%

Recombinant HE4 protein promotes proliferation of pancreatic and endometrial cancer cell lines

Chen

Senkowski

et al. 2015

Oncology Reports

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Abstract. Pancreatic adenocarcinoma is one of the most deadly malignancies, and endometrial cancer represents the most common gynecologic cancer in the USA. Better understanding on the pathologic mechanisms and pathways is required for effective treatment of these malignancies. Recently, human epididymis protein 4 (HE4 or WFDC2), a secretory glycoprotein, was found to be overexpressed in pancreatic and endometrial cancers. In addition, studies have shown that HE4 overexpression in endometrial cancer cell lines led to faster cancer progression in a mouse subcutaneous model. These findings raise a question on the role(s) of secretory, extracellular HE4 in cancer development. In the present study, we found that treatment of pancreatic and endometrial cancer cell lines with purified, extracellular HE4 protein led to a significant increase in cell viability and proliferation. Moreover, extracellular HE4 protein was able to increase DNA synthesis, and modulate the mRNA and protein levels of cell cycle marker PCNA and cell cycle inhibitor p21. These effects appeared to be robust and sustainable and required a relatively low concentration of HE4 protein. The findings indicated the secreted, extracellular HE4 may carry some physiopathological functions. Via paracrine/endocrine actions, circulatory HE4 produced by malignant cells may contribute to pancreatic and endometrial cancer progression and/or metastasis.

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Section: Introductionmentioning

confidence: 89%

Recombinant HE4 protein promotes proliferation of pancreatic and endometrial cancer cell lines

Chen

Senkowski

et al. 2015

Oncology Reports

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“…Inclusion of preoperative serum HE4 levels into the diagnostic Risk of Ovarian Malignancy Algorithm (ROMA) results in demonstrably improved specificity and sensitivity in detection and monitoring of the disease over Cancer Antigen 125 (CA 125), pelvic sonography, and menopausal status alone [5]. Research has also shown its ability to support EOC pathogenesis, including the promotion of proliferation, chemoresistance, antiestrogen resistance, adhesion, invasion, and migration [6][7][8][9][10][11][12][13][14][15][16][17]. One oncogenic pathway that has consistently been shown to interact with HE4 in several studies is the extracellular signal regulated kinase (ERK) pathway.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of DUSP6 sensitizes ovarian cancer cells to chemotherapeutic agents via regulation of ERK signaling response genes

et al. 2019

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Dual specificity phosphatase 6 (DUSP6) is a protein phosphatase that deactivates extracellular-signal-regulated kinase (ERK). Since the ovarian cancer biomarker human epididymis protein 4 (HE4) interacts with the ERK pathway, we sought to determine the relationship between DUSP6 and HE4 and elucidate DUSP6's role in epithelial ovarian cancer (EOC). Viability assays revealed a significant decrease in cell viability with pharmacological inhibition of DUSP6 using (E/Z)-BCI hydrochloride in ovarian cancer cells treated with carboplatin or paclitaxel, compared to treatment with either agent alone. Quantitative PCR was used to evaluate levels of ERK pathway response genes to BCI in combination with recombinant HE4 (rHE4), carboplatin, and paclitaxel. Expression of EGR1, a promoter of apoptosis, was higher in cells co-treated with BCI and paclitaxel or carboplatin than in cells treated with chemotherapeutic agents alone, while expression of the proto-oncogene c-JUN was decreased with co-treatment. The effect of BCI on the expression of these two genes opposed that of rHE4. Pathway focused quantitative PCR also revealed suppression of ERBB3 in cells co-treated with BCI plus carboplatin or paclitaxel. Finally, expression levels of DUSP6 in EOC tissue were evaluated by immunohistochemistry, revealing significantly increased levels of DUSP6 in serous EOC tissue compared to adjacent normal tissue. A positive correlation between HE4 and DUSP6 levels was determined by Spearman Rank correlation. In conclusion, DUSP6 inhibition sensitizes ovarian cancer cells to chemotherapeutic agents and alters gene expression of ERK response genes, suggesting that DUSP6 could plausibly function as a novel therapeutic target to reduce chemoresistance in EOC.

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“…The HE4 gene is important in regulating proliferation of serous ovarian cancer cells. HE4 may be involved in regulation of the cell cycle …”

Section: Introductionmentioning

confidence: 99%

“…A few studies have provided evidence of the cellular and molecular mechanisms that may underlie the role of HE4 in ovarian cancer progression. 10,11 HE4 gene silencing causes G0/G1 arrest and blocks the progression from the G1 to S phase. 10 The HE4 gene is important in regulating proliferation of serous ovarian cancer cells.…”

Section: Introductionmentioning

confidence: 99%

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Role of human epididymis protein 4 in chemoresistance and prognosis of epithelial ovarian cancer

Lee

Choi

Lee

et al. 2016

J of Obstet and Gynaecol

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Effect of WFDC 2 silencing on the proliferation, motility and invasion of human serous ovarian cancer cells in vitro

Cited by 30 publications

References 13 publications

Recombinant HE4 protein promotes proliferation of pancreatic and endometrial cancer cell lines

Recombinant HE4 protein promotes proliferation of pancreatic and endometrial cancer cell lines

Inhibition of DUSP6 sensitizes ovarian cancer cells to chemotherapeutic agents via regulation of ERK signaling response genes

Role of human epididymis protein 4 in chemoresistance and prognosis of epithelial ovarian cancer

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