Changes in Tumor Growth and Metastatic Capacities of J82 Human Bladder Cancer Cells Suppressed by Down-Regulation of Calreticulin Expression

Lu, Yi-Chien; Chen, Chiung-Nien; Wang, Bo-Jeng; Hsu, Wen Ming; Chen, Szu-Ta; Chang, King‐Jen; Chang, Cheng-Chi; Lee, Hsinyu

doi:10.1016/j.ajpath.2011.05.015

Cited by 40 publications

(42 citation statements)

References 46 publications

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“…Details of the CRT-knockdown human bladder cancer cell line J82 (J82 CRT-RNAi) have been described previously [18]. J82 CRT-RNAi cells were infected with pLKO_AS2.zeo-EGFP and selected with 250 μg/ml zeocin to generate J82 CRT-RNAi-GFP cells.…”

Section: Cell Culture and Generation Of Stably Transfected Cell Linesmentioning

confidence: 99%

Calreticulin activates β1 integrin via fucosylation by fucosyltransferase 1 in J82 human bladder cancer cells

Chen

Chu

et al. 2014

Biochemical Journal

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Fucosylation regulates various pathological events in cells. We reported that different levels of CRT (calreticulin) affect the cell adhesion and metastasis of bladder cancer. However, the precise mechanism of tumour metastasis regulated by CRT remains unclear. Using a DNA array, we identified FUT1 (fucosyltransferase 1) as a gene regulated by CRT expression levels. CRT regulated cell adhesion through α1,2-linked fucosylation of β1 integrin and this modification was catalysed by FUT1. To clarify the roles for FUT1 in bladder cancer, we transfected the human FUT1 gene into CRT-RNAi stable cell lines. FUT1 overexpression in CRT-RNAi cells resulted in increased levels of β1 integrin fucosylation and rescued cell adhesion to type-I collagen. Treatment with UEA-1 (Ulex europaeus agglutinin-1), a lectin that recognizes FUT1-modified glycosylation structures, did not affect cell adhesion. In contrast, a FUT1-specific fucosidase diminished the activation of β1 integrin. These results indicated that α1,2-fucosylation of β1 integrin was not involved in integrin-collagen interaction, but promoted β1 integrin activation. Moreover, we demonstrated that CRT regulated FUT1 mRNA degradation at the 3'-UTR. In conclusion, the results of the present study suggest that CRT stabilized FUT1 mRNA, thereby leading to an increase in fucosylation of β1 integrin. Furthermore, increased fucosylation levels activate β1 integrin, rather than directly modifying the integrin-binding sites.

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Section: Cell Culture and Generation Of Stably Transfected Cell Linesmentioning

confidence: 99%

Calreticulin activates β1 integrin via fucosylation by fucosyltransferase 1 in J82 human bladder cancer cells

Chen

Chu

et al. 2014

Biochemical Journal

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“…CRT is a calciumbinding protein that is crucial for many cellular processes (4). High levels of CRT are significantly associated with poor outcome and metastasis in patients with gastric cancer (5), bladder cancer (6), and breast cancer (7,8). Several observations show that CRT overexpression contributes to cancer cell survival, migration, and invasion (9), but the underlying molecular mechanisms are poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Calreticulin Promotes Migration and Invasion of Esophageal Cancer Cells by Upregulating Neuropilin-1 Expression via STAT5A

Feng

Pan

et al. 2014

Clinical Cancer Research

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Purpose: We previously revealed that the calreticulin (CRT) gene is a candidate oncogene promoting cell migration and invasion and that neuropilin-1 (NRP1) is a possible effector downstream of CRT in esophageal squamous carcinoma cells. This study aims to explore the mechanisms underlying the migration and invasion of esophageal cancer cells regulated by CRT through NRP1.Experimental Design: Quantitative reverse-transcription polymerase chain reaction, Western blot analysis, chromatin immunoprecipitation, and reporter gene assays were used to investigate the relationship between CRT and NRP1. In vitro and in vivo assays were carried out to evaluate the effects of NRP1 on malignant phenotypes of ESCC cells and tumor metastasis in NOD/SCID mice. Immunohistochemistry was performed to analyze the expression of CRT and NRP1 in esophageal squamous cell carcinomas (ESCC).Results: Knockdown of CRT decreased the expression of NRP1. Inhibition of NRP1 reduced ESCC cell motility in vitro and experimental metastasis in vivo. Ectopic expression of NRP1 rescued the defects of cell migration and invasion in CRT-shRNA cells. CRT depletion inhibited STAT5A phosphorylation at the Y694 site via a CaMKII-independent pathway. Moreover, STAT5A directly regulated NRP1 transcription. Knockdown of CRT or NRP1 led to a downregulation of MMP2, MMP9, and FAK. Notably, positive correlation was found between CRT and NRP1 expression in ESCC tissues (P ¼ 5.87 Â 10 À5 ). CRT and NRP1 coexpression was significantly associated with lymph node metastasis (P ¼ 0.025). Conclusions: Our findings suggest that NRP1 is a critical downstream effector of CRT in promoting cell migration and invasion, which might contribute to the metastasis of ESCC.

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“…Furthermore, we confirmed the usefulness of identified AAbs as sero-diagnostic and/or -prognostic biomarkers for BC by dot-blot analysis. In the and attachment, in contrast to the overexpression of calreticulin which enhanced cell migration and attachment (28). In BC tissues, calreticulin expression was predominant in the cytoplasm of BC cells, and its expression was higher in BC cells than in normal cancer patients (2,5,9).…”

Section: Association Of Serum Igg Levels Of Anti-calreticulin and Mmpmentioning

confidence: 94%

Detection of tumor-associated antigens in culture supernatants using autoantibodiesin sera from patients with bladder cancer

Minami¹,

Nagashio²,

Ueda³

et al. 2014

Biomed. Res.

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Secreted proteins play essential roles in the process of tumorigenesis, and the analysis of tumorsecreted proteins has been suggested as a promising strategy for identifying cancer biomarkers. In this study, we performed proteomic analysis to identify proteins secreted from bladder cancer cell lines that are recognized by autoantibodies in sera from patients with bladder cancer. In addition, autoantibodies against the identified proteins were validated using a dot-blot array with sera from patients with bladder cancer and normal controls. As the results, we detected twenty-five and thirty-two immunoreactive spots in sera from patients with high-and low-grade bladder cancer, respectively. In addition, validation analysis revealed that serum IgG levels of anti-calreticulin and matrix metalloproteinase-2 (MMP2) autoantibodies were significantly higher in bladder cancer patients than in normal controls (both P < 0.05). Furthermore, the serum IgG level of anti-MMP2 autoantibody was significantly higher in patients with high-compared to low-grade bladder cancer (P < 0.05). On multivariate analysis, the serum IgG level of anti-MMP2 autoantibody was an independent predictor of cancer-specific survival (P < 0.05). Based on these findings, serum IgG levels of anti-calreticulin and MMP2 autoantibodies may be novel biomarker candidates for bladder cancer and its clinical outcome.Bladder cancer (BC) is the 7th most common cancer in men and the 17th most common in women in the world. The incidence of BC has been increasing in Japan, and it was about 20 and 5 per 100,000 Japanese males and females in 2002 (22). Approximately 75-85% of BC are diagnosed as non-muscle-invasive bladder cancer (NMIBC) at the first diagnosis, and around 70% of cases present as pTa, 20% as pT1, and 10% as carcinoma in situ lesions (23).NMIBC has a tendency to recur (50-70%) and may progress (10-20%) to a higher grade and/or muscleinvasive BC in time, which might lead to high cancer-specific mortality (46). The histological tumor grade is one of the clinical factors associated with outcomes of patients with NMIBC. High-grade NMIBC generally shows a more aggressive behavior than the low-grade form, and increases the risk of a poorer prognosis (3, 32). Due to the unfavorable prognosis associated with high-grade NMIBC, differential diagnosis between high-and low-grade NMIBC might be crucial for more appropriate follow-up and aggressive treatment. Cystoscopy and urine cytology are commonly used techniques for the diagnosis and surveillance of BC. Cystoscopy can identify most papillary and

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Changes in Tumor Growth and Metastatic Capacities of J82 Human Bladder Cancer Cells Suppressed by Down-Regulation of Calreticulin Expression

Cited by 40 publications

References 46 publications

Calreticulin activates β1 integrin via fucosylation by fucosyltransferase 1 in J82 human bladder cancer cells

Calreticulin activates β1 integrin via fucosylation by fucosyltransferase 1 in J82 human bladder cancer cells

Calreticulin Promotes Migration and Invasion of Esophageal Cancer Cells by Upregulating Neuropilin-1 Expression via STAT5A

Detection of tumor-associated antigens in culture supernatants using autoantibodiesin sera from patients with bladder cancer

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