Abstract
S100A14 is an EF-hand calcium-binding protein that has been reported to be involved in the progression of many malignancies. However, its role in ovarian cancer has not yet been clarified. In this study, we investigated the significance of S100A14 expression in epithelial ovarian cancers (EOCs) as well as it's mechanism of action. On both RNA and protein levels, S100A14 was overexpressed in transformed cells. Immunohistochemical staining demonstrated that S100A14 expression was associated with advanced stage (P<0.001) and poor tumor grade (P<0.001). Moreover, S100A14 overexpression was an independent prognostic factor for overall survival (HR = 4.53, P = 0.029). We also investigated S100A14's functional role by employing lentiviral-mediated overexpression and knockdown in EOC cells. S100A14 overexpression promoted cell proliferation, tumorigenesis, migration, and invasion, whereas S100A14 knockdown inhibited these properties. TOV112D cells that overexpressed S100A14 also exhibited greater tumor growth potential in xenografted mice. S100A14 promoted such a malignant phenotype in EOC cells through the PI3K/Akt pathway. Taken together, our data indicate that S100A14 has a crucial role in EOC progression, and its overexpression is associated with poor prognosis. Further study of S100A14's molecular mechanisms may lead to the development of a novel therapeutic target for ovarian cancer.
Highlights
Ovarian cancer is the leading cause of death from gynecological malignancies in developed countries [1]
We previously observed that the transcription level of S100A14 was upregulated 7.85-fold in three epithelial ovarian cancers (EOCs) cell lines by microarray analysis [17]
Reverse transcriptase-PCR (RT-PCR) and real-time PCR revealed thatS100A14 mRNA levels were abundantly expressed in ovarian cancer cell lines, except TOV112D, OVCA433, and YDOV-151, whereas S100A14 expression was almost undetectable in human ovarian surface epithelial (HOSE) cell lines (Fig. 1A)
Summary
Ovarian cancer is the leading cause of death from gynecological malignancies in developed countries [1]. Despite their clinical importance, little is known about the early stages of development for this neoplasm, largely owing to the absence of adequate animal models, the clinical inaccessibility of human ovaries, and the unfortunate paucity of symptoms until higher stages. EOCs are believed to originate from normal ovarian surface epithelium or from its derivatives, which include the crypts and inclusion cysts on the epithelial surface [2]. A series of recent evidence suggest that www.impactjournals.com/oncotarget ovarian high-grade serous carcinoma (HGSC) originates from the fimbrial portion of the fallopian tube, which has been termed “serous tubal intraepithelial carcinoma” (STIC) [3,4,5,6]. Understanding the molecular basis of EOC should significantly refine the diagnosis and management of these tumors and eventually lead to the development of more specific and more effective treatment modalities
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