Epithelial-mesenchymal transition of circulating tumor cells in prostate cancer is promoted by survivin

Abstract

Objective: Recent studies demonstrated that circulating tumor cells (CTCs) contribute to the metastasis of prostate cancer. Survivin knockout could inhibit epithelial-mesenchymal transition (EMT) and suppress several metastatic tumors. In this study, we examined the potential involvement of survivin in EMT in CTCs. Methods: CTCs were isolated from the peripheral blood of 100 patients with prostate cancer as EpCAM þ /CD45 À cells via FACS sorting and identified by immunofluorescence staining of prostate-specific antigen (PSA). CTCs and DU145 cells were transfected with survivin siRNA. Then, the levels of survivin, E-cadherin, and vimentin in CTCs and DU145 cells were detected via immunofluorescence staining, and the invasiveness of CTCs and DU145 cells was examined using a Transwell chamber. Results: The results revealed the abundant expression of PSA in the cytoplasm of CTCs. Transfection of survivin siRNA significantly decreased the levels of survivin and vimentin in CTCs and DU145, whereas that of E-cadherin was significantly increased, suggesting survivin plays an important role in EMT of CTCs. In addition, survivin siRNA significantly inhibited the invasiveness of CTCs and DU145 cells. Conclusions: Survivin plays an important role in EMT of CTCs in prostate cancer, which might mediate the metastasis and invasion of prostate cancer.

Anticancer activities of Brachydin C in human prostate tumor cells (DU145) grown in 2D and 3D models: Stimulation of cell death and downregulation of metalloproteinases in spheroids

“…Cell migration is a key characteristic of tumor invasion, metastasis, and angiogenesis, and it has been closely linked to a poor prognosis (Trindade et al, 2019). Tumor cells acquire a mesenchymal phenotype during epithelial–mesenchymal transition (EMT), when cell polarity and the connection to the basement membrane are lost and the capacity to breakdown extracellular matrix is acquired (Deezagi & Safari, 2020; Yang et al, 2020), allowing the cells to pass through the basement membrane and destroy the ECM using metalloproteinases before reaching the circulation (Roy et al, 2020). MMPs, in general, promote the degradation of several ECM components, and MMP9 and MMP11 , in particular, play key roles in tumor initiation and invasion (Pittayapruek et al, 2016).…”

Ethanol extract of Imperata Cylindrica leaves inhibits proliferation and migration of HSC-3 cell lines

“…24 A previous study showed that inhibition of EMT promoters, the epithelial cell adhesion molecule (EpCAM) and survivin-1 also inhibit cancer cell migration. 25 Based on the qualitative phytochemical assay, the I. cylindrica leaf extract that is used in this research contains flavonoid, steroid, terpenoid, tannin and alkaloid. In carcinogenesis, flavonoid are secondary plant metabolites that have the ability to decrease proliferation, metastasis and angiogenesis and to increase apoptosis by interfering in multiple signal transducing pathways.…”

Promotion of ubiquitination-dependent survivin destruction contributes to xanthohumol-mediated tumor suppression and overcomes radioresistance in human oral squamous cell carcinoma

“…As the smallest member of the IAP family protein, survivin is frequently overexpressed in human cancers, including lung [24], prostate [25], colorectal [25], breast [26], ovarian [27], and liver [28] cancer. Previous studies have revealed that beyond regulation of cell division and mitosis, overexpression of survivin in cancer cells inhibits both extrinsic and intrinsic apoptosis signaling.…”

“…Importantly, the C-terminus of survivin is dispensable for cell division, whereas the N-terminus is required for apoptosis [29]. Moreover, a high level of survivin is related to enhanced angiogenesis, tumor invasion and metastasis, and chemo/radioresistance, and downregulation of survivin reversed these functions [25,30,31]. For example, overexpression of survivin confers insulin-like growth factor-induced lapatinib resistance in head and neck squamous carcinoma cells (HNSCC) [32].…”