Periostin Mediates TGF-β-Induced Epithelial Mesenchymal Transition in Prostate Cancer Cells

Abstract

Background: In our previous study, we found that periostin was upregulated in prostate cancer, and its expression could be modulated by TGF-β. TGF-β could upregulate periostin expression in some cells, and both TGF-β and periostin could induce epithelial mesenchymal transition (EMT). We aimed to study the effect of periostin in the process of TGF-β-induced EMT in prostate cancer cells. Methods: We constructed a lentivirus vector containing the periostin gene and transduced it into PC3 and DU145 cells. After confirming periostin overexpression by PCR and Western blotting, we used an MTT assay to establish a growth curve to measure cell proliferation. Additionally, we performed transwell and wound healing assays to measure cell invasion and migration, respectively. Lastly, we measured the expression of EMT associated factors using Western blot analysis to test the effect of periostin on EMT in prostate cancer cells. Results: PCR and Western blot analyses confirmed that periostin was upregulated after infection with the periostin lentiviral vector. Periostin overexpression promoted increased cell proliferation, invasion, and migration as measured by MTT, transwell, and wound healing assays, respectively. Western blot analysis illustrated that periostin overexpression increased the expression of EMT associated factors, and periostin overexpression activated Akt and GSK-3β, which could be inhibited using a PI3K inhibitor. Additionally, TGF-β increased the levels of STAT3, Twist1 and periostin, while both STAT3 shRNA and Twist1 shRNA inhibited periostin expression. However, STAT3 shRNA also decreased Twist1 expression. Although reduction of STAT3, Twist1 or periostin levels with shRNA inhibited TGF-β-induced overexpression of EMT associated factors, periostin overexpression could reverse such inhibition by interfering with STAT3 and Twist1. Similarly, periostin overexpression also reversed inhibition of cell invasion induced by interference of STAT3 and Twist1. Conclusion: Our findings indicate that periostin is an important mediator of TGF-β-induced EMT and suggest that periostin is a potential therapeutic target for suppressing the metastatic progression of prostate cancer.

The concomitant apoptosis and EMT underlie the fundamental functions of TGF-β

“…Both apoptotic and EMT responses to TGF-β treatment in PC3 and DU145 prostate cancer cells has been observed in separate studies [49][50][51], which suggests that a concomitant apoptosis and EMT may also occur in response to TGF-β in these cells. In the concomitant apoptosis and EMT, accumulating data have shown that the extent of both events can be modulated by either pro-survival and/ or pro-apoptotic factors.…”

“…Nevertheless, it is becoming more evident that TGF-β-induced apoptosis is associated with its induction of EMT in normal cells. For instance, as mentioned previously, TGF-β-induced apoptosis concomitantly occurs with EMT in hepatocytes, breast cells, renal cells, and prostate cells [33,34,37,38,[44][45][46][47][48][49]. TGF-β can induce EMT without an apoptotic response in many cancer cells, including pancreatic cancer cells [53][54][55] and lung cancer cells [56][57][58], and in immortal non-cancer cell lines such as Mv1Lu [31,32], MDCK [35,59], MCF10A [43], and HMEC [60].…”

Predictive and prognostic value of serum periostin in advanced non–small cell lung cancer patients receiving chemotherapy

“…21 An increasing number of studies have shown that periostin over-expression presents in various malignant tumors and closely relates with disease progression. In vitro and in vivo researches demonstrated that periostin participate in key processes in cancer metastasis such as cancer stem cell maintenance, 22 tumor cell survival, 5 protumoral macrophages recruitment, 23 pre-metastatic niche formation, 24 epithelial mesenchymal transition (EMT), 25 and angiogenesis. 26 Increased periostin levels have been detected in serum of patients with some malignant tumors.…”

Periostin promotes migration and invasion of renal cell carcinoma through the integrin/focal adhesion kinase/c-Jun N-terminal kinase pathway

“…2 Our previous study showed that POSTN could induce EMT of prostate cancer cells through PI3K/Akt/ GSK-3 beta signaling pathways. 16 In RCC, POSTN was elevated in stromal fibroblasts and enhanced ccRCC cell attachment. 17 However, the involvement of POSTN in other biological processes such as migration and invasion of RCC is still unclear.…”