Over-expression of TRPM8 is associated with poor prognosis in urothelial carcinoma of bladder

Xiao, Ni; Jiang, Lei; Ge, Bo; Zhang, Tian Yi; Zhao, Xiao K.; Zhou, Xing

doi:10.1007/s13277-014-2480-1

Cited by 23 publications

(24 citation statements)

References 22 publications

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“…Besides prostate carcinoma, the expression levels of TRPM8 were significantly higher in urothelial carcinoma of bladder tissues than in non-cancerous urothelial tissues [ 60 ]. A positive association between the expression levels of TRPM8 and histological grade or tumor stage was established.…”

Section: Trpm8 Channels In Cancersmentioning

confidence: 99%

Roles of TRPM8 Ion Channels in Cancer: Proliferation, Survival, and Invasion

Yee¹

2015

Cancers

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The goal of this article is to provide a critical review of the transient receptor potential melastatin-subfamily member 8 (TRPM8) in cancers, with an emphasis on its roles in cellular proliferation, survival, and invasion. The TRPM8 ion channels regulate Ca2+ homeostasis and function as a cellular sensor and transducer of cold temperature. Accumulating evidence has demonstrated that TRPM8 is aberrantly expressed in a variety of malignant solid tumors. Clinicopathological analysis has shown that over-expression of TRPM8 correlates with tumor progression. Experimental data have revealed important roles of TRPM8 channels in cancer cells proliferation, survival, and invasion, which appear to be dependent on the cancer type. Recent reports have begun to reveal the signaling mechanisms that mediate the biological roles of TRPM8 in tumor growth and metastasis. Determining the mechanistic roles of TRPM8 in cancer is expected to elucidate the impact of thermal and chemical stimuli on the formation and progression of neoplasms. Translational research and clinical investigation of TRPM8 in malignant diseases will help exploit these ion channels as molecular biomarkers and therapeutic targets for developing precision cancer medicine.

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Section: Trpm8 Channels In Cancersmentioning

confidence: 99%

Roles of TRPM8 Ion Channels in Cancer: Proliferation, Survival, and Invasion

Yee¹

2015

Cancers

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“…Previous studies have reported on the associations between certain cancer types and TRPM ion channels (7,(15)(16)(17)(18)(19)(20)(21); however, to the best of our knowledge, there have been no studies in the literature that have investigated the role of these ion channels in bladder cancer. In this original study, we aimed to determine whether bladder cancer is associated with the mRNA expression levels of TRPM ion channel genes, and whether this could merit further study with the aim of establishing novel treatment modalities.…”

Section: Introductionmentioning

confidence: 99%

Potential role of melastatin-related transient receptor potential cation channel subfamily M gene expression in the pathogenesis of urinary bladder cancer

et al. 2016

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Abstract. Urinary bladder cancer is one of the most common malignancies of the urinary tract. Ion channels and calcium homeostasis are involved in almost all basic cellular mechanisms. The transient receptor potential cation channel subfamily M (TRPM) takes its name from the melastatin protein, which is classified as potential tumor suppressor. To the best of our knowledge, there have been no previous studies in the literature investigating the role of these ion channels in bladder cancer. The present study aimed to determine whether bladder cancer is associated with mRNA expression levels of TRPM ion channel genes, and whether there is the potential to conduct further studies to establish novel treatment modalities. The present study included a total of 47 subjects, of whom 40 were bladder cancer patients and 7 were controls. Following the histopathological evaluation for bladder carcinoma, the mRNA and protein expression of TRPM were examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry in tumor and normal tissues, in order to determine whether there is a difference in the expression of these channels in tumor and normal tissues. Immunoreactivity for TRPM2, TRPM4, TRPM7 and TRPM8 was observed in epithelial bladder cells in the two groups. RT-qPCR revealed a significant increase in TRPM7 expression in bladder cancer tissue compared to the controls (healthy bladder tissue), whereas no differences in TRPM2 or TRPM4 expression levels were observed. There were significant reductions in the expression levels of TRPM5 and TRPM8 in bladder cancer tissues. In the present study, the effects of TRP ion channels on the formation of bladder cancer was investigated. This study is instructive for TRPM2, TRPM4, TRPM5, TRPM7 and TRPM8 and their therapeutic role in bladder cancer. The results support the fact that these gens can be novel targets and can also be tested for during the treatment of bladder cancer.

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“…The expression levels of TRPM8 mRNA in bladder tissue from urothelial carcinoma subjects were also significantly higher than those in matched noncancerous tissues (P = 0.016) (Xiao et al, 2014). Expression of the TRPM8 protein in bladder tissue from urothelial carcinoma subjects was significantly and positively associated with histological grade (P = 0.039) and tumor stage (P = 0.037) (Xiao et al, 2014). Significant correlation has been found between high TRPM8 expression and poor cumulative survival in patients with urothelial carcinoma of the bladder, suggesting that overexpression of TRPM8 may play a role in the pathogenesis and progression of the disease (Xiao et al, 2014).…”

Section: Discussionmentioning

confidence: 90%

“…Moreover, TRPM8 has higher expression in prostate cancer tissue than in normal prostate tissue, and has also been detected in tumors of the breast, colon, lung, skin, and pancreas (Tsavaler et al, 2001;Yee et al, 2010;Okamoto et al, 2012). The expression levels of TRPM8 mRNA in bladder tissue from urothelial carcinoma subjects were also significantly higher than those in matched noncancerous tissues (P = 0.016) (Xiao et al, 2014). Expression of the TRPM8 protein in bladder tissue from urothelial carcinoma subjects was significantly and positively associated with histological grade (P = 0.039) and tumor stage (P = 0.037) (Xiao et al, 2014).…”

Section: Discussionmentioning

confidence: 90%

“…Expression of the TRPM8 protein in bladder tissue from urothelial carcinoma subjects was significantly and positively associated with histological grade (P = 0.039) and tumor stage (P = 0.037) (Xiao et al, 2014). Significant correlation has been found between high TRPM8 expression and poor cumulative survival in patients with urothelial carcinoma of the bladder, suggesting that overexpression of TRPM8 may play a role in the pathogenesis and progression of the disease (Xiao et al, 2014). However, the relationship between TRPM8 and diabetes is still unclear.…”

Section: Discussionmentioning

confidence: 99%

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Expression of TRPM8 in diabetic rats and its relationship with visceral pain stimulation

Liu

et al. 2016

Genet. Mol. Res.

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ABSTRACT. Transient receptor potential cation channel, subfamily M, member 8 (TRPM8) is a nonselective cation channel and a candidate for cold sensation signaling, but the relationship between TRPM8 and diabetes remains unclear. In the present study, we determined the expression levels of TRPM8 messenger RNA (mRNA) and the levels of the TRPM8 protein in the bladder tissue of diabetic rats. We also investigated the correlation between TRPM8 expression and the visceral pain stimulation-related factor, calcitonin gene-related peptide (CGRP) in diabetic rats. The rats were sacrificed 3, 5, 7, and 15 days after streptozotocin injection, and blood was collected from their tail veins to determine the blood glucose levels. Bladder tissue was removed to assess the expression of TRPM8 mRNA by reverse transcription-polymerase chain reaction, and the expression of the TRPM8 protein by western blotting. After administering electrical stimulation (5 V/1 Hz), the expression levels of TRPM8 and CGRP proteins were determined. Our results revealed that the blood glucose level, and TRPM8 mRNA and TRPM8 protein expression levels increased significantly in the diabetic rats. Spinal tissue protein expression levels of both TRPM8 and CGRP also increased significantly following electrical stimulation. This possibly indicates that TRPM8 is closely associated with visceral pain stimulation, and could be an independent prognostic biomarker for diabetes.

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Over-expression of TRPM8 is associated with poor prognosis in urothelial carcinoma of bladder

Cited by 23 publications

References 22 publications

Roles of TRPM8 Ion Channels in Cancer: Proliferation, Survival, and Invasion

Roles of TRPM8 Ion Channels in Cancer: Proliferation, Survival, and Invasion

Potential role of melastatin-related transient receptor potential cation channel subfamily M gene expression in the pathogenesis of urinary bladder cancer

Expression of TRPM8 in diabetic rats and its relationship with visceral pain stimulation

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