Overexpression of SOX18 promotes prostate cancer progression via the regulation of TCF1, c-Myc, cyclin D1 and MMP-7

Abstract

Sex determining region Y (SRY)-box 18 (SOX18) gene encodes transcription factors that have been recently confirmed to be overexpressed in various human types of cancer and maintain the malignant behavior of cancer cells. However, the role and its potential function in prostate cancer (PCa) has not been demonstrated and the mechanisms of SOX18 involved in tumor progression remain largely unclear. In the present study, the expression of SOX18 was analyzed in 98 PCa and 81 adjacent non-tumor tissues using immunohistochemistry. The data showed that SOX18 was overexpressed in 72 of 98 (73.5%) PCa tissues compared with that in 28 of 81 (34.6%) non-tumor tissues. In addition, the expression of SOX18 was related with the clinical features of patients with PCa. To explore the potential role of SOX18 in PCa cells, Cell Counting Kit-8 (CCK-8), migration, invasion and xenograft assays were performed. Our data showed that knockdown of SOX18 decreased the proliferation, migration and invasion of PCa cells in vitro, in addition to the tumor growth in vivo. Markedly, SOX18 knockdown caused the decreased expression of TCF1, c-Myc, cyclin D1 and MMP-7. In conclusion, SOX18 was overexpressed in PCa and may regulate the malignant capacity of cells via the upregulation of TCF1, c-Myc, cyclin D1 and MMP-7.

12(S)-HETE induces lymph endothelial cell retraction in�vitro by upregulation of SOX18

“…Thus, future screening approaches in search of SOX18/PROX1 inhibitors are required and may reveal compounds with improved specificity. SOX18 overexpression is observed in different cancer types (12)(13)(14)(15)(16)(17)(18) causing enhanced migration, adhesion and invasivity (45). This underscores the importance to determine specific SOX18-targeting strategies (20).…”

“…SOX18 directly regulates (among other target genes) the transcription of prospero homeobox protein 1 (PROX1), which itself determines the differentiation from blood vessels to lymphatic vessels during embryonic development (7)(8)(9)(10)(11). Furthermore, as SOX18 is overexpressed in various cancer entities (12)(13)(14)(15)(16)(17)(18), this additionally renders SOX18 a candidate target to block vascularisation and metastasis. Thus, a screening approach was undertaken to identify small molecules that inhibit SOX18.…”

Influence of miR-7a and miR-24-3p on the SOX18 transcript in lung adenocarcinoma

“…Our preliminary studies have shown a disparity in the amount of SOX18 mRNA relative to the quantity of protein (25)(26)(27), which may be associated with the regulation of the translation by microRNAs (miRNAs). This has allowed us to hypothesize that the SOX18 transcript level is subject to control by miRNA molecules, since similar mechanisms are observed in many other types of tumors in relation to different types of proteins, as for example miRNA-34b in prostate cancer (28,29). miRNAs are involved in many important biological processes, such as proliferation, cell differentiation, apoptosis, embryogenesis and organogenesis.…”

Plasma levels of MMP-7 and TIMP-1 in laboratory diagnostics and differentiation of selected histological types of epithelial ovarian cancers

“…MMP-7 (matrilysin) is the smallest proteinase from the entire metalloproteinases family with broad proteolytic activity against proteoglycans, elastin, laminin, collagens [19]. Overexpression and increased serum levels of this metalloproteinase have been confirmed in prostate, lung, renal, colorectal or breast malignancies [20–24]. Some clinical studies have also revealed significantly elevated TIMP-1 levels in the plasma of patients with colorectal, prostate and pancreatic cancers, which was associated with worse clinical outcomes [25–27].…”