Abstract
Human epididymis protein 4 (HE4) is an important clinical biomarker used for the detection of epithelial ovarian cancer (EOC). While much is known about the predictive power of HE4 clinically, less has been reported regarding its molecular role in the progression of EOC. A deeper understanding of HE4’s mechanistic functions may help contribute to the development of novel targeted therapies. Thus far, it has been difficult to recommend HE4 as a therapeutic target owing to the fact that its role in the progression of EOC has not been extensively evaluated. This review summarizes what is collectively known about HE4 signaling and how it functions to promote tumorigenesis, chemoresistance, and metastasis in EOC, with the goal of providing valuable insights that will have the potential to aide in the development of new HE4-targeted therapies.
Highlights
22,280 new cases of epithelial ovarian cancer (EOC) are diagnosed each year, resulting in 14,240 deaths annually in the United States [1]
Integrin β5 (ITGβ5) gene expression was differentially regulated by Human epididymis protein 4 (HE4) in ES-2 and CaOV3 cells, which was confirmed by positive correlation of ITGB5 and HE4 staining in paraffin embedded ovarian tissue samples [10]
Loss of DAG1 is associated with cancer progression [85]. These results show that HE4 is strongly interconnected with ECM related proteins, those involved in the ITGβ5 signaling pathway
Summary
Human epididymis protein 4 (HE4) is an important clinical biomarker used for the detection of epithelial ovarian cancer (EOC). While much is known about the predictive power of HE4 clinically, less has been reported regarding its molecular role in the progression of EOC. A deeper understanding of HE4’s mechanistic functions may help contribute to the development of novel targeted therapies. It has been difficult to recommend HE4 as a therapeutic target owing to the fact that its role in the progression of EOC has not been extensively evaluated. This review summarizes what is collectively known about HE4 signaling and how it functions to promote tumorigenesis, chemoresistance, and metastasis in EOC, with the goal of providing valuable insights that will have the potential to aide in the development of new HE4-targeted therapies
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