Autoproteolysis of the SEA module of rMuc3 C-terminal domain modulates its functional composition

Peng, Zhihong; He, Yonghong; Yang, Yongtao; Zhu, Rong; Bai, Jianying; Li, Yicheng; Yu, Hao; Zhang, Xin; Chen, Lei; Chen, Wensheng; Fang, Dian‐Chun; Wang, Rongquan

doi:10.1016/j.abb.2010.08.013

Cited by 7 publications

(15 citation statements)

References 34 publications

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“…Because the extracellular domain of MUC17 protein contains several EGF-like functional domains, reduction of MUC17 expression by rs10953316 SNP may down-regulate the erbB signaling leading to inhibition of cell proliferation [ 23 ]. In addition, SEA domain at the C-terminal region of MUC17 is critical for its autoproteolysis, which controls cell migration and invasion [ 31 ]. These studies provide clues for us to presume that rs10953316 SNP plays a protective role in endometriosis development by reducing total MUC17 expression and the downstream signaling, whereas the detailed mechanism remains to be further investigated.…”

Section: Discussionmentioning

confidence: 99%

Genetic variations of MUC17 are associated with endometriosis development and related infertility

et al. 2015

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BackgroundGenetic alterations of mucin genes, such as MUC2 and MUC4, were previously identified to be associated with endometriosis and related infertility. Additionally, gene expression profiling has confirmed MUC17 to be overexpressed in mucinous ovarian carcinoma; however, its associated risk for endometriosis remains unclear. This study was focused on the potential impact of genetic variations in MUC17 on endometriosis development and associated clinical features.MethodsThe study subjects included 189 female Taiwanese patients with pathology-proven endometriosis and 191 healthy Taiwanese women as controls. Five single-nucleotide polymorphisms (rs4729645, rs10953316, rs74974199, rs4729655, and rs4729656) within the MUC17 gene were selected and genotyped using the Taqman genotyping assay to examine the allele frequency and genotype distributions of MUC17 polymorphisms.ResultsGenotyping revealed that the A allele at rs10953316 in MUC17 was a protective genetic factor in endometriosis development (p = 0.008; OR = 0.53; 95 % CI: 0.36-0.79). Genetic variation of rs4729655 protected patients against endometriosis-induced infertility, but was associated with a higher cancer antigen 125 (CA125) level. Base-pairing analysis, called MaxExpect, predicted an additional loop in the mRNA structure caused by rs10953316 polymorphism, possibly influencing ribosome sliding and translation efficiency. Such predictions were confirmed by immunohistochemistry that patients with AA genotype at rs10953316 showed low MUC17 levels in their endometrium, patients with GA genotype showed moderate levels, and strong staining could be found in patients with GG genotype.ConclusionsMUC17 polymorphisms are involved in endometriosis development and the associated infertility in the Taiwanese population.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-015-0209-7) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Genetic variations of MUC17 are associated with endometriosis development and related infertility

et al. 2015

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“…Epigenetically, expression of MUC3A is contributed by promoter hypomethylation [46] . Cysteine-rich domains of MUC3 promote cell migration and inhibit apoptosis [47] , and the MUC3 C-terminal domain undergoes autoproteolysis at its SEA module, which maintains its availability for potentiation of signaling modulated by HER/ErbB2 phosphorylation to promote migration and invasion [48] . Enhanced MUC3 expression by a tetrameric branched peptide with a conserved TFLK motif inhibits bacteria adherence [49] , and expression of MUC3 is altered in inflammatory bowel disease and correlated with disease activity and the extent of inflammation [50] .…”

Section: Discussionmentioning

confidence: 99%

A Comprehensive Expression Analysis of Mucins in Appendiceal Carcinoma in a Multicenter Study: MUC3 Is a Novel Prognostic Factor

et al. 2014

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BackgroundMucins are implicated in survival in various cancers, but there have been no report addressed on survival in appendiceal carcinoma, an uncommon disease with different clinical and pathological features from those of other colon cancers. We aimed to investigate the clinical implications of expression of mucins in appendiceal carcinoma.MethodsExpression profiles of MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC6, MUC16 and MUC17 in cancer tissue were examined by immunohistochemistry in 108 cases of surgically resected appendiceal carcinoma.ResultsThe following relationships of mucins with clinicopathologic factors were identified: MUC1 with positive lymphatic invasion (p = 0.036); MUC2 with histological type (mucinous carcinoma, p<0.001), superficial invasion depth (p = 0.007), negative venous invasion (p = 0.003), and curative resection (p = 0.019); MUC3 with non-curative resection (p = 0.017); MUC5AC with histological type (mucinous carcinoma, p = 0.002), negative lymphatic invasion (p = 0.021), and negative venous invasion (p = 0.022); and MUC16 with positive lymph node metastasis (p = 0.035), positive venous invasion (p<0.05), and non-curative resection (p = 0.035). A poor prognosis was related to positive lymph node metastasis (p = 0.04), positive lymphatic invasion (p = 0.02), positive venous invasion (p<0.001), non-curative resection (p<0.001), and positive expression of MUC3 (p = 0.004). In multivariate analysis, positive venous invasion (HR: 6.93, 95% CI: 1.93–24.96, p = 0.003), non-curative resection (HR: 10.19, 95% CI: 3.05–34.07, p<0.001) and positive MUC3 expression (HR: 3.37, 95% CI: 1.13–10.03, p = 0.03) were identified as significant independent prognostic factors in patients with appendiceal carcinoma.ConclusionsExpression of MUC3 in appendiceal carcinoma is an independent factor for poor prognosis and a useful predictor of outcome in patients with appendiceal carcinoma after surgery.

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“…MUC3A adjusted cell migration and apoptosis through tyrosine phosphorylation of two EGF cysteine-rich domains [20]. Similar to MUC1, SEA module at the C-terminal domain of MUC3A was critical for its autoproteolysis to impact migration and invasion by HER/ErbB2 phosphorylation [21]. In addition, MUC3A expression may regulated by PKC signal pathway and therefore modulated the invasive and metastatic properties in cancer cells [22].…”

Section: Discussionmentioning

confidence: 99%

Increased expression of MUC3A is associated with poor prognosis in localized clear-cell renal cell carcinoma

et al. 2016

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MUC3A is a membrane-associated mucin that recent evidence reveals the role of MUC3A in pathogenesis and progression of cancers. To evaluate the association between MUC3A expression with overall survival (OS) and recurrence-free survival (RFS) in patients with localized clear-cell renal cell carcinoma (ccRCC), we retrospectively detected MUC3A expression in samples of 384 postoperative localized ccRCC patients by immunohistochemistry. Median follow-up was 73 months (range: 42 – 74 mo). Overall, 41 patients died, 47 experienced recurrence. High MUC3A expression occurred in 45.8% of localized ccRCC cases, which was significantly associated with high pT-stage, high Fuhrman grade, high frequency of necrosis and LVI, and increased risk of recurrence and death (Logrank test P < 0.001 and P < 0.001, respectively). By multivariate analysis, MUC3A expression was confirmed as an adverse independent prognostic factor for OS and RFS. The prognostic accuracy of UISS, SSIGN, Leibovich models was significantly increased when MUC3A expression was integrated. Meanwhile, MUC3A was enrolled into a newly built nomogram with other factors selected by multivariate analysis. Calibration curves revealed optimal consistency between observations and prognosis. In conclusion, high MUC3A expression is an adverse prognostic biomarker for OS and RFS in postoperative localized ccRCC patients.

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Autoproteolysis of the SEA module of rMuc3 C-terminal domain modulates its functional composition

Cited by 7 publications

References 34 publications

Genetic variations of MUC17 are associated with endometriosis development and related infertility

Genetic variations of MUC17 are associated with endometriosis development and related infertility

A Comprehensive Expression Analysis of Mucins in Appendiceal Carcinoma in a Multicenter Study: MUC3 Is a Novel Prognostic Factor

Increased expression of MUC3A is associated with poor prognosis in localized clear-cell renal cell carcinoma

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