Growth differentiation factor-15: a p53- and demethylation-upregulating gene represses cell proliferation, invasion and tumorigenesis in bladder carcinoma cells

Tsui, Ke-Hung; Hsu, Shu-Yuan; Chung, Li-Chuan; Lin, Yu‐Hsiang; Feng, Tsui-Hsia; Lee, Tzu‐Yi; Chang, Phei‐Lang; Juang, Horng‐Heng

doi:10.1038/srep12870

Cited by 59 publications

(42 citation statements)

References 42 publications

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“…Maspin belongs to the serine protease inhibitor/noninhibitor superfamily and has dissimilar effects according to the types of cancer [4]. Although reports concerning the biological function of maspin in bladder cancer are still contradictory, our previous studies have indicated that maspin is the downstream gene of the prostate-derived Ets factor (PDEF) and growth differentiation factor 15 (GDF15), which are antitumor genes in bladder carcinoma cells [18,19].…”

Section: Discussionmentioning

confidence: 99%

“…The expression vector with full-length human maspin cDNA was purchased from Invitrogen. Electroporation was conducted with the ECM 830 system (BTX, San Diego, CA, USA) by setting the voltage at 180 V, setting the pulse length at 90 milliseconds, and using a single pulse setting, as described in a previous method [18]. The mock-transfection cells were transfected with a control of a pcDNA3 expression vector and clonally selected in the same manner as the gene-overexpressed cells.…”

Section: Expression Vector Constructs and Stable Transfectionmentioning

confidence: 99%

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Maspin is a PTEN-Upregulated and p53-Upregulated Tumor Suppressor Gene and Acts as an HDAC1 Inhibitor in Human Bladder Cancer

Lin

Tsui

Chang

et al. 2019

Cancers

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Maspin is a member of the clade B serine protease inhibitor superfamily and exhibits diverse regulatory effects in various types of solid tumors. We compared the expressions of maspin and determined its potential biological functions and regulatory mechanisms in bladder carcinoma cells in vitro and in vivo. The results of RT-qPCR indicated that maspin expressed significantly lower levels in the bladder cancer tissues than in the paired normal tissues. The immunohistochemical assays of human bladder tissue arrays revealed similar results. Maspin-knockdown enhanced cell invasion whereas the overexpression of maspin resulted in the opposite process taking place. Knockdown of maspin also enhanced tumorigenesis in vivo and downregulated protein levels of acetyl-histone H3. Moreover, in bladder carcinoma cells, maspin modulated HDAC1 target genes, including cyclin D1, p21, MMP9, and vimentin. Treatment with MK2206, which is an Akt inhibitor, upregulated maspin expression, whereas PTEN-knockdown or PTEN activity inhibitor (VO-OHpic) treatments demonstrated reverse results. The ectopic overexpression of p53 or camptothecin treatment induced maspin expression. Our study indicated that maspin is a PTEN-upregulated and p53-upregulated gene that blocks cell growth in vitro and in vivo, and may act as an HDAC1 inhibitor in bladder carcinoma cells. We consider that maspin is a potential tumor suppressor gene in bladder cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Expression Vector Constructs and Stable Transfectionmentioning

confidence: 99%

Maspin is a PTEN-Upregulated and p53-Upregulated Tumor Suppressor Gene and Acts as an HDAC1 Inhibitor in Human Bladder Cancer

Lin

Tsui

Chang

et al. 2019

Cancers

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“…The NDRG1 (−4714 to +46) reporter vectors were constructed as described previously51. A 5.2 kbp DNA fragment was subtracted from a BAC clone (PR11-998D10; Invitrogen) and cloned into the pGEM-3 vector (Promega BioScience) with the Kpn I cutting site.…”

Section: Methodsmentioning

confidence: 99%

Lipocalin 2 (LCN2) is a promising target for cholangiocarcinoma treatment and bile LCN2 level is a potential cholangiocarcinoma diagnostic marker

Chiang

Yeh

et al. 2016

Sci Rep

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Cholangiocarcinoma (CCA) is a devastating disease due to resistance to traditional chemotherapies and radiotherapies. New therapeutic strategies against CCA are urgently needed. This study investigated the role of lipocalin-2 (LCN2) in human cholangiocarcinoma as a potential therapeutic target and diagnostic marker. So far, the role of LCN2 in cancer is still controversial and studies regarding the role of LCN2 in CCA are limited. LCN2 knockdown inhibited CCA cell growth in vitro and in vivo through induction of cell cycle arrest at G0/G1 phases and decreased metastatic potential due to repression of epithelial-mesenchymal transition (EMT). Overexpression of LCN2 in CCA cells increased cell metastatic potential. We showed for the first time that the N-myc downstream regulated gene 1 (NDRG1) and NDRG2, known as tumor suppressor genes, are negatively regulated by LCN2 in CCA cells. LCN2 concentration in bile was higher in patients with CCA than that in patients with gallstones, with a cutoff value of 20.08 ng/ml making this a potential diagnostic marker. Higher LCN2 expression was associated with worse survival in patients with CCA. LCN2 is a promising target for CCA treatment and bile LCN2 level is a potential diagnostic marker for CCA.

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“…NAG-1 expression reduces TNF-α secretion in macrophages [10], and ectopic expression of NAG-1 causes cell growth arrest [6, 8]. Furthermore, overexpression of NAG-1 in human colon, bladder, and glioblastoma cells inhibits tumor formation in the nude mouse model [4, 6, 110]. The principal function, receptor, and signaling pathway of NAG-1 remain uncertain in cancer, and the biological role of NAG-1 in diseases remains poorly understood with sometimes contradictory evidence.…”

Section: Secreted Proteins (Mmps and Nag-1)mentioning

confidence: 99%

Moonlighting proteins in cancer

2016

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Since the 1980s, growing evidence suggested that the cellular localization of proteins determined their activity and biological functions. In a classical view, a protein is characterized by the single cellular compartment where it primarily resides and functions. It is now believed that when proteins appear in different subcellular locations, the cells surpass the expected activity of proteins given the same genomic information to fulfill complex biological behavior. Many proteins are recognized for having the potential to exist in multiple locations in cells. Dysregulation of translocation may cause cancer or contribute to poorer cancer prognosis. Thus, quantitative and comprehensive assessment of dynamic proteins and associated protein movements could be a promising indicator in determining cancer prognosis and efficiency of cancer treatment and therapy. This review will summarize these so-called moonlighting proteins, in terms of a coupled intracellular cancer signaling pathway. Determination of the detailed biological intracellular and extracellular transit and regulatory activity of moonlighting proteins permits a better understanding of cancer and identification of potential means of molecular intervention.

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Growth differentiation factor-15: a p53- and demethylation-upregulating gene represses cell proliferation, invasion and tumorigenesis in bladder carcinoma cells

Cited by 59 publications

References 42 publications

Maspin is a PTEN-Upregulated and p53-Upregulated Tumor Suppressor Gene and Acts as an HDAC1 Inhibitor in Human Bladder Cancer

Maspin is a PTEN-Upregulated and p53-Upregulated Tumor Suppressor Gene and Acts as an HDAC1 Inhibitor in Human Bladder Cancer

Lipocalin 2 (LCN2) is a promising target for cholangiocarcinoma treatment and bile LCN2 level is a potential cholangiocarcinoma diagnostic marker

Moonlighting proteins in cancer

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