Profilin 1 overexpression in renal cell carcinoma

Minamida, Satoru; Kodera, Yasuhiro; Kawashima, Yusuke; Ikeda, Masaomi; Okusa, Hiroshi; Fujita, Tetsuo; Maeda, Tadakazu; Baba, Shirō

doi:10.1111/j.1442-2042.2010.02670.x

Cited by 31 publications

(24 citation statements)

References 28 publications

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“…An interesting point with respect to Pfn1 expression is similar to what Minamida et al (48) reported: we found Pfn1 overexpression in RCC tissues and cell lines. In contrast, Pfn1 has been found to be underexpressed in most, if not all, aggressive adenocarcinomas.…”

Section: Discussionsupporting

confidence: 91%

“…Interestingly, all 29 proteins had previously been reported to be involved in tumor progression and metastasis (Table I and supplemental Table S6). For example, two proteins that we identified as dysregulated in our study, Pfn1 and agmatinase, were also reported to have increased (48) or decreased (49,50) expression in RCC. In addition, many of the proteins we reported had been shown to be involved in cellular migration and invasion.…”

Section: Discussionmentioning

confidence: 52%

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Quantitative Proteomic Analysis in Metastatic Renal Cell Carcinoma Reveals a Unique Set of Proteins with Potential Prognostic Significance

Masui

White

DeSouza

et al. 2013

Molecular & Cellular Proteomics

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Metastatic renal cell carcinoma (RCC) is one of the most treatment-resistant malignancies, and patients have a dismal prognosis, with a <10% five-year survival rate. The identification of markers that can predict the potential for metastases will have a great effect in improving patient outcomes. In this study, we used differential proteomics with isobaric tags for relative and absolute quantitation (iTRAQ) labeling and LC-MS/MS analysis to identify proteins that are differentially expressed in metastatic and primary RCC. We identified 1256 non-redundant proteins, and 456 of these were quantified. Further analysis identified 29 proteins that were differentially expressed (12 overexpressed and 17 underexpressed) in metastatic and primary RCC. Dysregulated protein expressions of profilin-1 (Pfn1), 14 -3-3 zeta/delta (14 -3-3), and galectin-1 (Gal-1) were verified on two independent sets of tissues by means of Western blot and immunohistochemical analysis. Hierarchical clustering analysis showed that the protein expression profile specific for metastatic RCC can distinguish between aggressive and non-aggressive RCC. Pathway analysis showed that dysregulated proteins are involved in cellular processes related to tumor progression and metastasis. Furthermore, preliminary analysis using a small set of tumors showed that increased expression of Pfn1 is associated with poor outcome and is a potential prognostic marker in RCC. In addition, 14 -3-3 and Gal-1 also showed higher expression in tumors with poor prognosis than in those with good prognosis. Dysregulated proteins in metastatic RCC represent potential prognostic markers for kidney cancer patients, and a greater understanding of their involved biological pathways can serve as the foundation of the development of novel targeted therapies for metastatic RCC. Molecular

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 52%

Quantitative Proteomic Analysis in Metastatic Renal Cell Carcinoma Reveals a Unique Set of Proteins with Potential Prognostic Significance

Masui

White

DeSouza

et al. 2013

Molecular & Cellular Proteomics

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“…PFN1 was first reported as a breast cancer tumor inhibitor several years ago by Janke et al (41). Since then, PFN1 has been widely reported as a potential tumor suppressor in a variety of malignant tumors, such as skin fibrosarcoma (42), pancreatic ductal adenocarcinoma (43), hepatocellular carcinoma (44) and renal carcinoma (45). The function of PFN1 has gradually been revealed in recent years as in vitro studies on PFN1 have now been undertaken in several breast cancer cell lines.…”

Section: Discussionmentioning

confidence: 99%

Decreased expression of profilin 2 in oral squamous cell carcinoma and its clinicopathological implications

Zhang

2011

Oncol Rep

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Abstract. Profilins are small proteins essential for many normal cellular dynamics and constitute one of the crucial components of actin-based cellular motility. Several recent studies have implicated a role for the profilin (PFN) family in cancer pathogenesis and progression. However, their expression and promising functions are largely unknown in oral squamous cell carcinoma (OSCC). In this study, we analyzed the correlation between PFN1 and PFN2 expression in vitro and in vivo. The protein expression levels were roughly compared between cell lines (HIOEC, HB96) with the employment of mass spectrometry. PFN2 was singled out as one of the significantly down-regulated genes in the cancerous HB96 cells. The expression levels of PFN1 and PFN2 in vitro were validated by RT-PCR, real-time PCR and Western blotting. Laser scanning confocal microscopy was used for the first time to assess the localization of PFN2 expression. In subsequent experiments, we observed the relationship between PFN2 expression levels and the proliferation of transfected HB96 cancer cells. VASP, N-WASP and P27 expression was also examined in the PFN2-transfected or non-transfected HB96 cells. In vivo, antigen expression was determined by immunohistochemical analyses in 88 paired tissue specimens. Decreased protein expression was confirmed in cancerous tissues from 88 OSCC patients compared with paracancerous normal mucous epithelia. Tumors with weak PFN2 expression were associated with a significantly worse prognosis than strongly expressed tumours (P<0.001). Other statistical analyses were performed to assess the differences in expression and their clinical and pathological significance. In conclusion, PFN2 can be utilized as both a potential suppressor marker and a prognostic protein for OSCC. The function of PFN2 may be to regulate the N-WASP/Arp2/3 signaling pathway. IntroductionOral squamous cell carcinoma (OSCC) is a significant public health problem with >300,000 new cases being diagnosed annually worldwide (1). The prognosis of OSCC remains relatively unfavorable, with the overall survival rate at 5 years oscillating between 40 and 55% (2,3). Further, it has been observed that ~40% of OSCC patients die from uncontrolled locoregional disease alone, and 24% show metastases to distant sites, even though more radical therapies have now been applied (4). Given the malignant nature of the disease, early detection and more effective therapies are urgently needed (5). However, a poor understanding of the biology of the disease, imperfect screening of biomarkers and the presence of only a few symptoms or warning signs in early-stage disease all contribute to treatment failure (6).Recent efforts have been focused on the discovery of particular biomarkers that can distinguish between the specific biological properties of normal and cancer cells (7). The extraordinary developments made in proteomic technologies in the past decade have enabled investigators to search for biomarkers by simply scanning through proteomic data (8). Perhaps the most wel...

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“…PFN-1 expression is down-regulated in breast cancer [12], bladder cancer [24], pancreatic cancer [9], and hepatocarcinoma [22], but is overexpressed in renal cell carcinoma [15]. PFN-1 is thought to be a potent tumor suppressor in breast cancer cells [21,25].…”

Section: Introductionmentioning

confidence: 99%

Overexpression of Profilin 1 Inhibited Ovarian Tumor Cell Growth and Migration

Lee¹

2017

Journal of Life Science

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Abnormal actin remodeling is a typical characteristic of tumor cells. Thymosin β10 (TB10) and profilin-1 (PFN-1) are actin-binding proteins and essential regulators of actin polymerization. We previously showed that TB10 induced death in ovarian cancer cells by sequestering F-actin, but the underlying mechanisms of this induction have not been explored. In this study, we identified TB10 as a novel regulator of PFN-1 and demonstrated its novel function as a tumor suppressor in ovarian cancer cell lines. The present study investigated protein expression profiles through polyacrylamide gel electrophoresis (PAGE) and liquid chromatography-mass spectroscopy (LC-MS/MS) in SKOV3 cells, an ovarian cancer cell line, that were transiently transfected with TB10. PFN-1 was highly overexpressed in response to TB10, and overexpression of PFN-1 resulted in inhibition of cell proliferation and migration and promotion of cellular apoptosis in ovarian cancer cells. Furthermore, transiently transfected PFN-1 appeared to deactivate the Erk signaling pathway, followed by decreased expression of Elk-1 and Egr-1 in human ovarian cancer cells. Interestingly, PFN-1 did not affect the activation of Akt. The results demonstrated that PFN-1 induced apoptotic cell death and inhibited proliferation and migration in ovarian cancer cells, suggesting that PFN-1 may be valuable in anti-cancer therapy.

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Profilin 1 overexpression in renal cell carcinoma

Cited by 31 publications

References 28 publications

Quantitative Proteomic Analysis in Metastatic Renal Cell Carcinoma Reveals a Unique Set of Proteins with Potential Prognostic Significance

Quantitative Proteomic Analysis in Metastatic Renal Cell Carcinoma Reveals a Unique Set of Proteins with Potential Prognostic Significance

Decreased expression of profilin 2 in oral squamous cell carcinoma and its clinicopathological implications

Overexpression of Profilin 1 Inhibited Ovarian Tumor Cell Growth and Migration

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