Syndecan‐1, a key regulator of cell viability in endometrial cancer

• Published in: International journal of cancer 2007-08, Vol.121 (4), p.741-750
• Main Authors: Choi, Dong Soon, Kim, Ji‐Hye, Ryu, Hee‐Sug, Kim, Hyon Chang, Han, Jae Ho, Lee, Jong Soo, Min, Churl K.
• Format: Article
• Language: English
• Subjects: Apoptosis; apoptotic cell death; Biological and medical sciences; Cell Line; Cell Line, Tumor; Cell Survival; endometrial cancers; Endometrial Neoplasms - metabolism; Endometrial Neoplasms - pathology; Endometrium - metabolism; Erk/Akt pathway; Extracellular Signal-Regulated MAP Kinases - metabolism; Female; Female genital diseases; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; Medical sciences; Phosphorylation; Proto-Oncogene Proteins c-akt - metabolism; PTEN Phosphohydrolase - metabolism; RNA Interference; Signal Transduction; Syndecan-1 - physiology; syndecan‐1; Tumors; Up-Regulation
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.22713

Syndecan‐1 is one of the major proteoglycans on cell surfaces involved in major biological processes. Although loss of syndecan‐1 correlates well with the gain of cancerous characteristics in a wide range of cancers, increased expression of syndecan‐1 also coincides with adverse outcomes in some cancers, including breast, ovarian and pancreatic cancers. For this Janus‐faced attitude of syndecan‐1, we sought to examine expression patterns of syndecan‐1 in endometrial carcinoma (EC) and gain insight into the roles of syndecan‐1. Immunohistochemical examinations of 109 endometrial tissue samples from myoma, hyperplasia and EC uteri revealed that syndecan‐1 expression was significantly upregulated in EC compared with hyperplasia (p < 0.001). To evaluate pathophysiological functions of syndecan‐1, its expression level was altered, and subsequent outcomes were examined using human endometrial cancer cell lines such as HEC‐1A, AN3CA and KLE cells. Overexpression of syndecan‐1 increased the growth of HEC‐1A cells regardless of anchorage dependence while silencing syndecan‐1 by antisense RNAs caused apoptotic cell death. Consistent with decreased viability, the loss of syndecan‐1 was also accompanied by a decrease in the activation of Erk and Akt and a concomitant decrease in the phosphorylation of PTEN and PDK1, which are known as negative and positive regulators of Akt activation, respectively. These down‐regulatory effects were reversed upon overexpression of syndecan‐1. Collectively together, the aforementioned findings lend support to the notion that upregulation of syndecan‐1 may be a critical element for endometrial cancers in maintaining their viability and thus can serve as a cancer specific therapeutic and diagnostic marker. © 2007 Wiley‐Liss, Inc.