Protein isoform-specific validation defines multiple chloride intracellular channel and tropomyosin isoforms as serological biomarkers of ovarian cancer

Tang, Hsin‐Yao; Beer, Lynn A.; Tanyi, János L.; Zhang, Rugang; Liu, Qin; Speicher, David W.

doi:10.1016/j.jprot.2013.06.016

Cited by 76 publications

(75 citation statements)

References 47 publications

(57 reference statements)

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“…However, the existence of other TPM family members varied among the different types of cancers or studies (17)(18)(19). In the present study, TPM1 was significantly downregulated in most RCC tissues compared to that in the tumor adjacent normal renal tissues while TPM2-4 showed no significant expression differences in the RCC tissue samples.…”

Section: Discussioncontrasting

confidence: 50%

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

Wang

Jin

et al. 2015

Oncology Reports

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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...

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Section: Discussioncontrasting

confidence: 50%

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

Wang

Jin

et al. 2015

Oncology Reports

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“…In support of this, several LMSS proteins have been reported previously as circulating biomarkers in cancer patients, correlating to presence of cancer or associating with poor clinical outcome. As such, serum CLIC4 levels were elevated in ovarian cancer patients compared with controls (Tang et al 2013), LCP1 was increased in the plasma of patients with kidney cancer (Tang et al 2013), and the plasma GDF15 levels were high in colorectal cancer patients and predicted poor survival (Wallin et al 2011;Mehta et al 2015).…”

Section: Discussionmentioning

confidence: 95%

Identification of Nidogen 1 as a lung metastasis protein through secretome analysis

et al. 2017

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Secreted proteins play crucial roles in mediating tumor-stroma interactions during metastasis of cancer to different target organs. To comprehensively profile secreted proteins involved in lung metastasis, we applied quantitative mass spectrometry-based proteomics and identified 392 breast cancer-derived and 302 melanoma-derived proteins secreted from highly lung metastatic cells. The cancer-specific lung metastasis secretome signatures (LMSSs) displayed significant prognostic value in multiple cancer clinical data sets. Moreover, we observed a significant overlap of enriched pathways between the LMSSs of breast cancer and melanoma despite an overall small overlap of specific proteins, suggesting that common biological processes are executed by different proteins to enable the two cancer types to metastasize to the lung. Among the novel candidate lung metastasis proteins, Nidogen 1 (NID1) was confirmed to promote lung metastasis of breast cancer and melanoma, and its expression is correlated with poor clinical outcomes. In vitro functional analysis further revealed multiple prometastatic functions of NID1, including enhancing cancer cell migration and invasion, promoting adhesion to the endothelium and disrupting its integrity, and improving vascular tube formation capacity. As a secreted prometastatic protein, NID1 may be developed as a new biomarker for disease progression and therapeutic target in breast cancer and melanoma.

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“…Thus, TPM2 may be a biomarker candidate for CRC. Several early studies also showed that TPM2 was downregulated in human esophageal squamous cell carcinoma [34] and upregulated in ovarian cancer [35] and breast cancer [36]. TPM2 can be detected in the serum of ovarian cancer patients, and the TPM2 expression level is higher in the serum sample of ovarian cancer patients than in the serum sample of healthy volunteers [35].…”

Section: Discussionmentioning

confidence: 99%

iTRAQ-based quantitative analysis of cancer-derived secretory proteome reveals TPM2 as a potential diagnostic biomarker of colorectal cancer

Xiao

Shao

et al. 2016

Front. Med.

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Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. We aimed to find novel molecules as potential biomarkers for the early diagnosis of CRC. A serum-free conditioned medium was successfully collected from three pairs of CRC tissue and adjacent normal tissue. iTRAQ-based quantitative proteomic analysis was applied to compare the differences in secretome between primary CRC mucosa and adjacent normal mucosa. A total of 145 kinds of proteins were identified. Of these proteins, 29 were significantly different between CRC and normal tissue. Tropomyosin 2 β (TPM2) exhibited the most significant differences; as such, this protein was selected for further validation. Quantitative real-time PCR indicated that the mRNA expression of TPM2 significantly decreased in the CRC tissue compared with the paired adjacent normal tissue. Immunohistochemical analysis also confirmed that TPM2 was barely detected at protein levels in the CRC tissue. In summary, this study revealed potential molecules for future biomarker applications and provided an efficient approach for the differential analysis of cancer-associated secretome. TPM2 may be valuable for the early diagnosis of CRC.

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Protein isoform-specific validation defines multiple chloride intracellular channel and tropomyosin isoforms as serological biomarkers of ovarian cancer

Cited by 76 publications

References 47 publications

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

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

Identification of Nidogen 1 as a lung metastasis protein through secretome analysis

iTRAQ-based quantitative analysis of cancer-derived secretory proteome reveals TPM2 as a potential diagnostic biomarker of colorectal cancer

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