MUC5AC protects pancreatic cancer cells from TRAIL-induced death pathways

Hoshi, Hajime; Sawada, Tetsuji; Uchida, Motoyuki; Iijima, Hiroko; Kimura, Kenjiro; Hirakawa, Kosei; Wanibuchi, Hideki

doi:10.3892/ijo.2013.1760

Cited by 33 publications

(27 citation statements)

References 28 publications

(30 reference statements)

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“…An in vivo xenograft study by Hoshi et al [28] showed that MUC5AC knockdown drastically downregulated the tumorigenicity and suppressed the tumor growth. MUC5AC inhibits the antitumor effect of neutrophils and neutrophils-induced apoptosis [29]. It supports the MUC5AC functions as an immunosuppressive agent and plays a key role in the escape of carcinoma cells from immunosurveillance.…”

Section: Discussionsupporting

confidence: 53%

Evaluation of serum MUC5AC in combination with CA19-9 for the diagnosis of pancreatic cancer

et al. 2020

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Background: Pancreatic cancer (PC) is a highly aggressive tumor with a poor prognosis that lacks specific diagnostic markers. Mucin 5AC (MUC5AC) is a member of the mucin family, a heterogeneous group of high molecular weight, heavily glycosylated proteins that could be either membrane-bound or secreted. This multicentral study is to evaluate the performance of serum MUC5AC in combination with carbohydrate antigen 19-9 (CA19-9) for the diagnosis of PC in Asian. Methods: Sixty-one patients with PC (comprised of early pancreatic cancer [n = 30] and late pancreatic cancer [n = 31] patients), 29 benign control, 35 choledocholithiasis, 25 chronic pancreatitis, and 34 healthy controls, were recruited from two hospitals. Serum levels of MUC5AC were evaluated by commercial ELISA kits. CA19-9 was measured by chemiluminescence immunoassay. The cutoff value of MUC5AC was determined based on optimal sensitivity and specificity. Results: Serum MUC5AC in patients with ] ng/mL) presented higher levels than those in controls. The combined biomarker panel (MUC5AC and CA19-9) presented better performance and improved specificity to differentiate PC from controls (AUC 0.894; 95% CI (0.844-0.943), sensitivity 0.738, specificity 0.886) than CA19-9 (p = 0.043) or MUC5AC alone (p = 0.010); however, the latter two had no difference (p = 0.824). Conclusions: Serum MUC5AC is a potential biomarker for PC. The combination with CA19-9 presents improved specificity and better performance.

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Section: Discussionsupporting

confidence: 53%

Evaluation of serum MUC5AC in combination with CA19-9 for the diagnosis of pancreatic cancer

et al. 2020

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“…Studies characterizing the function of MUC5AC are scarce. Hoshi et al [84] showed that MUC5AC protects pancreatic cancer cells from TRAIL-induced apoptosis, while other reports suggest that MUC5AC has no effect on cell growth, cell survival, proliferation, or morphology in vitro [85].…”

Section: Discussionmentioning

confidence: 99%

Prognostic and Clinicopathological Significance of MUC Family Members in Colorectal Cancer: A Systematic Review and Meta-Analysis

Zuo

Liu

et al. 2019

Gastroenterology Research and Practice

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Objective. To assess the association between MUC expression levels in colorectal cancer (CRC) tissues and prognosis and investigate the associations between MUC expression levels and CRC clinicopathological characteristics. Methods. The PubMed, Embase, Cochrane Library, and Web of Science databases were searched from inception through September 13, 2019, to identify studies investigating the association between MUC expression levels in CRC tissues and prognosis. Pooled hazard ratios (HRs) or odds ratio (ORs) with 95% confidence intervals (CIs) were used to evaluate associations between MUC expression levels and prognosis or clinicopathological characteristics, respectively. The heterogeneity between studies was assessed by the I2 values, whereas the likelihood of publication bias was assessed by Egger’s linear regression and Begg’s rank correlation test. Results. Among 33 included studies (n=6032 patients), there were no associations between combined MUC phenotype expression levels and overall survival (OS) or disease-free survival (DFS)/relapse-free survival (RFS) in patients with CRC. In subgroup analyses, the upregulated MUC1 expression (HR=1.50; 95% CI, 1.29–1.74; P<0.00001) was associated with poor OS. However, the upregulated MUC2 expression (HR=0.64; 95% CI, 0.52–0.79; P<0.00001) was associated with better OS. Furthermore, a high level of MUC1 expression (HR=1.99; 95% CI, 0.99–3.99; P=0.05) was associated with shorter DFS/RFS. However, patients with a low level of MUC2 tumors showed better DFS/RFS than patients with a high level of MUC2 tumors (HR=0.71; 95% CI, 0.49–1.04; P=0.08; P=0.0.009, I2=67%) and MUC5AC expression (HR=0.56; 95% CI, 0.38–0.82; P=0.003) was associated with longer DFS/RFS. In addition, a high level of MUC1 expression was associated with CRC in the rectum, deeper invasion, lymph node metastasis, distant metastasis, advanced tumor stage, and lymphatic invasion. A high level of MUC2 expression had a protective effect. High secretion of MUC5AC is associated with colon cancer compared with rectal cancer. Conclusion. The protein expression of MUC1 might be a poor biomarker in colorectal cancer and might play a role in tumor transformation and metastasis. However, the protein expression of MUC2 expression might have a protective effect. Furthermore, randomized controlled trials (RCTs) of large patients are needed to confirm the results.

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“…However, till date the molecular mechanism of its functioning is still obscure. The knockdown studies revealed that MUC5AC overexpression in tumor cells is associated with increased growth, adhesion, invasion of tumor cells and increased metastatic tendency [25]–[27]. Further, it is associated with lower infiltration of B cells and neutrophils at metastatic sites [26].…”

Section: Discussionmentioning

confidence: 99%

Pathobiological Implications of Mucin (MUC) Expression in the Outcome of Small Bowel Cancer

et al. 2014

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Mucins have been associated with survival in various cancer patients, but there have been no studies of mucins in small bowel carcinoma (SBC). In this study, we investigated the relationships between mucin expression and clinicopathologic factors in 60 SBC cases, in which expression profiles of MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC6 and MUC16 in cancer and normal tissues were examined by immunohistochemistry. MUC1, MUC5AC and MUC16 expression was increased in SBC lesions compared to the normal epithelium, and expression of these mucins was related to clinicopathologic factors, as follows: MUC1 [tumor location (p = 0.019), depth (p = 0.017) and curability (p = 0.007)], MUC5AC [tumor location (p = 0.063) and lymph node metastasis (p = 0.059)], and MUC16 [venous invasion (p = 0.016) and curability (p = 0.016)]. Analysis of 58 cases with survival data revealed five factors associated with a poor prognosis: poorly-differentiated or neuroendocrine histological type (p<0.001), lymph node metastasis (p<0.001), lymphatic invasion (p = 0.026), venous invasion (p<0.001) and curative resection (p<0.001), in addition to expression of MUC1 (p = 0.042), MUC5AC (p = 0.007) and MUC16 (p<0.001). In subsequent multivariate analysis with curability as the covariate, lymph node metastasis, venous invasion, and MUC5AC and/or MUC16 expression were significantly related to the prognosis. Multivariate analysis in curative cases (n = 45) showed that SBC with MUC5AC and/or MUC16 expression had a significantly independent high hazard risk after adjusting for the effects of venous invasion (hazard ratio: 5.6, 95% confidence interval: 1.8–17). In conclusion, the study shows that a MUC5AC-positive and/or MUC16-positive status is useful as a predictor of a poor outcome in patients with SBC.

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MUC5AC protects pancreatic cancer cells from TRAIL-induced death pathways

Cited by 33 publications

References 28 publications

Evaluation of serum MUC5AC in combination with CA19-9 for the diagnosis of pancreatic cancer

Evaluation of serum MUC5AC in combination with CA19-9 for the diagnosis of pancreatic cancer

Prognostic and Clinicopathological Significance of MUC Family Members in Colorectal Cancer: A Systematic Review and Meta-Analysis

Pathobiological Implications of Mucin (MUC) Expression in the Outcome of Small Bowel Cancer

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