Higher Expression of Peroxisome Proliferator-activated Receptor γ or Its Activation by Agonist Thiazolidinedione-rosiglitazone Promotes Bladder Cancer Cell Migration and Invasion

Yang, Dong Rong; Lin, San‐Yih; Ding, Xian Fan; Miyamoto, Hiroshi; Messing, Edward M.; Li, Li Qiong; Wang, Nancy; Chang, Chawnshang

doi:10.1016/j.urology.2012.12.027

Cited by 27 publications

(35 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To provide a closer look at the impact of PPAR γ on bladder cell progression, Yang et al analyzed samples of both benign bladder and bladder cancer mucosal samples by fluorescence in situ hybridization (FISH) assay for expression of PPAR γ , and the authors found 31% (8/21 samples) of the bladder cancer mucosal samples and 4.3% (1/23 samples) of benign bladder samples showed amplification [58]. In addition, lower levels of PPAR γ amplification were detected in non-muscle-invasive bladder cancer samples compared to muscle-invasive samples (16.7% versus 46.7%, resp.)…”

Section: Pparγ and Bladder Cancermentioning

confidence: 99%

Deciphering the Roles of Thiazolidinediones and PPARγin Bladder Cancer

et al. 2017

View full text Add to dashboard Cite

The use of thiazolidinedione (TZD) therapy in type II diabetic patients has proven useful in the lowering of blood glucose levels. However, recent investigations have shown that there may be potential health concerns associated, including the risk of developing bladder cancer as well as complications in the cardiovasculature. TZDs are ligands for the nuclear receptor PPARγ, and activation causes lipid uptake and insulin sensitization, both of which are critical processes for diabetic patients whose bodies are unable to utilize insulin effectively. Several studies have shown that PPARγ/TZDs decrease IGF-1 levels and, thus, reduce cancer growth in carcinomas such as the pancreas, colon, liver, and prostate. However, other studies have shed light on the potential of the receptor as a biomarker for uroepithelial carcinomas, particularly due to its stimulatory effect on migration of bladder cancer cells. Furthermore, PPARγ may provide the tumor-promoting microenvironment by de novo synthesis of nutrients that are needed for bladder cancer development. In this review, we closely examine the TZD class of drugs and their effects on PPARγ in patient studies along with additional molecular factors that are positive modulators, such as protein phosphatase 5 (PP5), which may have considerable implications for bladder cancer therapy.

show abstract

Section: Pparγ and Bladder Cancermentioning

confidence: 99%

Deciphering the Roles of Thiazolidinediones and PPARγin Bladder Cancer

et al. 2017

View full text Add to dashboard Cite

show abstract

“…The major warning for Actos use is that long-term treatment may increase bladder cancer (BCa) risk. Yang et al (2013) also recently found that PPARg amplification was increased dramatically in BCa tissue compared with normal urothelium (38.1 vs 4.3%) and in tumors with lymph node metastasis compared with those without metastasis (75.0 vs 15.4%). Human BCa 5637 cells with strong PPARg expression had better cell migration and invasion abilities than the BCa UMUC-3 cells with weak PPARg expression.…”

Section: The Effects On the Pharmaceutical Industry/drug Developmentmentioning

confidence: 78%

“…Human BCa 5637 cells with strong PPARg expression had better cell migration and invasion abilities than the BCa UMUC-3 cells with weak PPARg expression. Knocking down PPARg in BCa 5637 cells led to decreased cell migration and activation of PPARg with TZDs promoted their migration and invasive ability, indicating that PPARg and its ligand TZD may play a positive role in promoting BCa progression (Yang et al 2013).…”

Section: The Effects On the Pharmaceutical Industry/drug Developmentmentioning

confidence: 98%

Differential roles of PPARγ vs TR4 in prostate cancer and metabolic diseases

Liu

Lin

et al. 2014

Endocrine-Related Cancer

Self Cite

View full text Add to dashboard Cite

Peroxisome proliferator-activated receptor g (PPARg, NR1C3) and testicular receptor 4 nuclear receptor (TR4, NR2C2) are two members of the nuclear receptor (NR) superfamily that can be activated by several similar ligands/activators including polyunsaturated fatty acid metabolites, such as 13-hydroxyoctadecadienoic acid and 15-hydroxyeicosatetraenoic acid, as well as some anti-diabetic drugs such as thiazolidinediones (TZDs). However, the consequences of the transactivation of these ligands/activators via these two NRs are different, with at least three distinct phenotypes. First, activation of PPARg increases insulin sensitivity yet activation of TR4 decreases insulin sensitivity. Second, PPARg attenuates atherosclerosis but TR4 might increase the risk of atherosclerosis. Third, PPARg suppresses prostate cancer (PCa) development and TR4 suppresses prostate carcinogenesis yet promotes PCa metastasis. Importantly, the deregulation of either PPARg or TR4 in PCa alone might then alter the other receptor's influences on PCa progression. Knocking out PPARg altered the ability of TR4 to promote prostate carcinogenesis and knocking down TR4 also resulted in TZD treatment promoting PCa development, indicating that both PPARg and TR4 might coordinate with each other to regulate PCa initiation, and the loss of either one of them might switch the other one from a tumor suppressor to a tumor promoter. These results indicate that further and detailed studies of both receptors at the same time in the same cells/organs may help us to better dissect their distinct physiological roles and develop better drug(s) with fewer side effects to battle PPARg-and TR4-related diseases including tumor and cardiovascular diseases as well as metabolic disorders.

show abstract

“…Certain previous studies have reported that PPARγ is able to induce anti-proliferative, anti-angiogenic and pro-differentiation signaling pathways in specific tissue types, thus serving a role in the pathogenesis and progression of various types of cancer, including prostate cancer (24,25). Using TZDs as PPARγ ligands, previous studies have investigated the effect of PPARγ on the metastatic potential and investigated its underlying mechanisms (26)(27)(28)(29)(30)(31)(32)(33)(34). TZDs have been demonstrated to be able to suppress cellular migration, invasion and metastasis of cancer in the colon, liver, breast, lung, bladder and prostate gland (26)(27)(28)(29)(30)(31)(32)(33)(34).…”

Section: Discussionmentioning

confidence: 99%

“…Using TZDs as PPARγ ligands, previous studies have investigated the effect of PPARγ on the metastatic potential and investigated its underlying mechanisms (26)(27)(28)(29)(30)(31)(32)(33)(34). TZDs have been demonstrated to be able to suppress cellular migration, invasion and metastasis of cancer in the colon, liver, breast, lung, bladder and prostate gland (26)(27)(28)(29)(30)(31)(32)(33)(34). For example, in colon cancer, TZD inhibited the development and metastasis of HT-29 human colon cancer cells via its differentiation-promoting effects both in vivo and in vitro by involving the modulation of the E-cadherin/β-catenin system (26).…”

Section: Discussionmentioning

confidence: 99%

Troglitazone inhibits the migration and invasion of PC‑3 human prostate cancer cells by upregulating E‑cadherin and glutathione peroxidase 3

Chang

Lee

et al. 2018

Oncol Lett

View full text Add to dashboard Cite

Abstract. Troglitazone (TGZ) is a synthetic peroxisome proliferator-activated receptor γ (PPARγ) ligand that exhibits potential antitumor effects on a number of cancer subtypes, including prostate cancer. However, little is known about the effect of TGZ on metastasis in prostate cancer. The aim of the present study was to determine the inhibitory effect and mechanism underlying TGZ on cell growth, migration and invasion using the prostate cancer PC-3 cell line. Cellular migration and invasion were evaluated by performing a wound healing assay and Matrigel assay, respectively. The expression levels of mRNA and protein were determined by reverse transcription-quantitative polymerase chain reaction and western blotting. The results demonstrated that TGZ dose-dependently inhibited cell migration and invasion of PC-3 cells. The present study also revealed that TGZ increased the mRNA and protein levels of E-cadherin and glutathione peroxidase 3 (GPx3) in human prostate cancer PC-3 cells. In addition, GW9662, a PPARγ antagonist, attenuated the increased mRNA and protein levels of E-cadherin and GPx3, suggesting that the PPARγ-dependent signaling pathway was involved. Taken together, these results suggested that the anti-migration and anti-invasion effect of TGZ on PC-3 prostate cancer cells is, at least in part, mediated via upregulation of E-cadherin and GPx3. The present study also concluded that PPARγ may be used as a potential remedial target for the prevention and treatment of prostate cancer cell invasion and metastasis.

show abstract

Higher Expression of Peroxisome Proliferator-activated Receptor γ or Its Activation by Agonist Thiazolidinedione-rosiglitazone Promotes Bladder Cancer Cell Migration and Invasion

Cited by 27 publications

References 17 publications

Deciphering the Roles of Thiazolidinediones and PPARγin Bladder Cancer

Deciphering the Roles of Thiazolidinediones and PPARγin Bladder Cancer

Differential roles of PPARγ vs TR4 in prostate cancer and metabolic diseases

Troglitazone inhibits the migration and invasion of PC‑3 human prostate cancer cells by upregulating E‑cadherin and glutathione peroxidase 3

Contact Info

Product

Resources

About