Clinical and tumor significance of tropomyosin-1 expression levels in renal cell carcinoma

Abstract

Abstract. Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults and has been described as one of the deadliest of cancers affecting the genitourinary tract. Tropomyosin is a two-stranded α-helical coiled coil protein found in cell cytoskeletons. One of its isoforms, tropomyosin-1 (TPM1) has been reported as a novel tumor-suppressor gene and is downregulated in many solid tumors. However the expression level and function of TPM1 in RCC have not yet been determined. In the present study, we evaluated the TPM1-4 mRNA and TPM1 protein levels in RCC tissue samples. TPM1-overexpressing OSRC-2 and 786-O cell lines were also used to investigate the impact of TPM1 on RCC cells. We found that TPM1 was significantly and specifically downregulated in the RCC tissues. TPM1 expression was associated with tumor size, smoking status, Fuhrman grade and the prognosis of RCC patients. After TPM1 transfection, the migratory and invasive abilities of the OSRC-2 and 786-O cell lines were both reduced when compared to the control groups. Meanwhile, apoptosis was also enhanced in these two RCC cell lines following TPM1 transfection. Taken together, TPM1 exhibits characteristics of a tumor-suppressor gene while being overexpressed in RCC cell lines. IntroductionRenal cell carcinoma (RCC), which originates from renal tubular epithelial cells, accounts for 80-85% of all cases of kidney cancer, and is responsible for ~2-3% of all malignant diseases in adults (1). The overall 5-year survival of RCC is as low as 20-25%, and the most important factor in the selection of the appropriate therapy for RCC patients is the presence of metastases (2).Tropomyosin (TPM) is an important component of microfilaments, a cytoskeleton structure, and is mainly involved in the contraction of skeletal and smooth muscle cells or maintaining the stability of the cytoskeleton in non-muscular cells (3). Four tropomyosin genes, TPM1, TPM2, TPM3 and TPM4, have been confirmed in mammals including humans. More than 20 isoforms can be produced through alternative splicing. All of these homologous isoforms fold into two parallel, linear chains of spiral α-helices (4). These TPM proteins are involved in the regulation of many benign myopathies, such as myasthenia gravis and familial hypertrophic cardiomyopathy (5). Additionally, other studies have discovered that TPM1 plays an important role as a tumor-suppressor gene (TSG) in tumor occurrence and progression (6,7). Recently, evidence indicates that TPM1 could be a novel target gene of microRNA-21 which was found to be upregulated in many different solid tumors, including RCC (8). However, whether or not TPM1 serves as a tumor-suppressor gene in RCC and is selectively downregulated during RCC development has not been determined. Therefore, in the present study, we investigated the expression level of TPM1 in a set of RCC tissue samples and further evaluated its tumor-suppressing activities in two RCC cell lines (786-O and OSRC-2). Materials and methodsTissue samples. Ninety-eight tissue samples in...

Global Quantitative Proteomics reveal Deregulation of Cytoskeletal and Apoptotic Signalling Proteins in Oral Tongue Squamous Cell Carcinoma

“…Thus, to define the function of proteins involved in cytoskeletal reorganization is crucial to understand the mechanism behind the malignant progression of cancers. While cofilins are reported to modulate G-actin/F-actin ratio by binding directly to the actin filaments and affect the actin dynamics 49 , the tropomyosin family of proteins form an important component of intermediate filaments and help in the contraction of skeletal and smooth muscle cells or maintaining the cytoskeletal stability in non-muscular cells 50 . In contrast, the myosin light chain family of proteins are known to regulate myofilament activation via phosphorylation by Ca 2+ dependent myosin light chain kinase 51 .…”

Long non-coding RNA MEG3 suppresses the development of bladder urothelial carcinoma by regulating miR-96 and TPM1

“…22 Previous studies showed that TPM1 expression was associated with tumor size, smoking status, Fuhrman grade and the prognosis of renal cell carcinoma (RCC) patients. 23 It was also proposed to be a crucial tumor suppressor, which exhibited a low expression level in many solid tumors. 24,25 However, TPM1 exon 6a was found exclusively included in the prostate cancer samples but preferentially included in bladder cancer samples, which enlightened us a possible controversy of its role.…”

Genome‐wide screening of abberant methylated drivers combined with relative risk loci in bladder cancer

“…TPM1 and TPM2 are both members of tropomyosin (TPM) family, which discovered as a category of actin binding proteins acting as inhibitors of cellular transformation . Previous research reported that overexpression of TPM1 was related to a larger tumor size and a higher tumor grade, and TPM1 was proved as a potential biomarker of renal cell carcinoma prognosis . Unlike TPM1, poorly TPM2 were identified associated with malignant progression prostate tumors .…”