Overexpression of MUC15 activates extracellular signal-regulated kinase 1/2 and promotes the oncogenic potential of human colon cancer cells

Huang, John; Che, Mei-Ieng; Huang, Yu‐Ting; Shyu, Ming‐Kwang; Huang, Yuming; Wu, Yao‐Ming; Lin, Wei‐Chou; Huang, Pei‐Hsin; Liang, Jin–Tung; Lee, Po‐Huang; Huang, Min-Chuan

doi:10.1093/carcin/bgp137

Cited by 48 publications

(46 citation statements)

References 23 publications

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“…MUC15 is cell membrane-associated mucin. MUC15 overexpression in colorectal carcinoma cells enhances cell proliferation, cell extracellular matrix adhesion, colony-forming ability, and invasion (37). SPAG11B is a cationic secretory anti-microbial peptide expressed in human epididymis (38,39).…”

Section: Discussionmentioning

confidence: 99%

Verification of Male Infertility Biomarkers in Seminal Plasma by Multiplex Selected Reaction Monitoring Assay

Drabovich

Jarvi

Diamandis

2011

Molecular & Cellular Proteomics

103

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Seminal plasma is a promising biological fluid to use for noninvasive clinical diagnostics of male reproductive system disorders. To verify a list of prospective male infertility biomarkers, we developed a multiplex selected reaction monitoring assay and measured the relative abundance of 31 proteins in 30 seminal plasma samples from normal, nonobstructive azoospermia and post-vasectomy individuals. Median levels of some proteins were decreased by more than 100-fold in nonobstructive azoospermia or post-vasectomy samples, in comparison with normal samples. To follow up the most promising candidates and measure their concentrations in seminal plasma, heavy isotope-labeled internal standards were synthesized and used to reanalyze 20 proteins in the same set of samples. Concentrations of candidate proteins in normal seminal plasma were found in the range 0.1-1000 g/ml but were significantly decreased in nonobstructive azoospermia and post-vasectomy. These data allowed us to select, for the first time, biomarkers to discriminate between normal, nonobstructive azoospermia, and post-vasectomy (simulated obstructive azoospermia) seminal plasma samples. Some testis-specific proteins (LDHC, TEX101, and SPAG11B) performed with absolute or nearly absolute specificities and sensitivities. Cell-specific classification of protein expression indicated that Sertoli or germ cell dysfunction, but not Leydig cell dysfunction, was observed in nonobstructive azoospermia seminal plasma. The proposed panel of biomarkers, pending further validation, could lead to a clinical assay that can eliminate the need for testicular biopsy to diagnose the category of male infertility, thus providing significant benefits to patients as well as decreased costs associated with the differential diagnosis of azoospermia. Molecular & Cellular Proteomics 10: 10.1074/mcp.M110.004127, 1-13, 2011.Human infertility affects ϳ15% of couples, with the male contributing to the infertility in 50% of all cases (1, 2). One of the most severe forms of male infertility is azoospermia, which is characterized by an absence of sperm in the semen (3). Azoospermia is diagnosed in 20% of subfertile men and has two forms: obstructive azoospermia (OA) 1 and nonobstructive azoospermia (NOA). OA is caused by a physical obstruction in the male reproductive tract. The biological outcome of OA is thus identical to that of vasectomy, which is a surgical severance of the vas deferens. NOA is a more complicated infertility syndrome with the azoospermia being secondary to a failure to produce sperm; NOA may be further subclassified as maturation arrest, Sertoli cell-only syndrome, and hypospermatogenesis (4).For most men with azoospermia, testicular biopsy is the only currently used method to definitively distinguish between OA and NOA (5, 6). Thus, there is an urgent need for an alternative noninvasive approach with better diagnostic potential. The differential diagnosis of normal, NOA, and OA (or post-vasectomy (PV)) men is required for the following reasons: (i) in infertile pati...

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Section: Discussionmentioning

confidence: 99%

Verification of Male Infertility Biomarkers in Seminal Plasma by Multiplex Selected Reaction Monitoring Assay

Drabovich

Jarvi

Diamandis

2011

Molecular & Cellular Proteomics

103

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“…Increased MUC1 expression at the invasive front in CRC correlates with poor prognosis [280]. Overexpression of MUC15 enhances cell proliferation, cell-ECM adhesion, colony-forming ability and invasion in HCT116 cells [281].…”

Section: Mucinsmentioning

confidence: 99%

The Tumor Microenvironment in Colorectal Carcinogenesis

Peddareddigari

Wang

DuBois

2010

Cancer Microenvironment

186

163

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Colorectal cancer is the second leading cause of cancer-related mortality in the United States. Therapeutic developments in the past decade have extended life expectancy in patients with metastatic disease. However, metastatic colorectal cancers remain incurable. Numerous agents that were demonstrated to have significant antitumor activity in experimental models translated into disappointing results in extending patient survival. This has resulted in more attention being focused on the contribution of tumor microenvironment to the progression of a number of solid tumors including colorectal cancer. A more complete understanding of interactions between tumor epithelial cells and their stromal elements will enhance therapeutic options and improve clinical outcome. Here we will review the role of various stromal components in colorectal carcinogenesis and discuss the potential of targeting these components for the development of future therapeutic agents.

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“…Cell invasion assays were done in BioCoat Matrigel Invasion Chambers (Becton Dickinson) according to the manufacturer's protocol, as previously described (17). Briefly, 500 mL DMEM with or without chemoattractants was loaded in the lower part of the chamber and 3 Â 10 4 of transfected cells in 500 mL serumfree DMEM were seeded onto the upper part.…”

Section: Matrigel Invasion Assaymentioning

confidence: 99%

Mucin Glycosylating Enzyme GALNT2 Regulates the Malignant Character of Hepatocellular Carcinoma by Modifying the EGF Receptor

Liu²,

Hu³

et al. 2011

Cancer Research

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Extracellular glycosylation is a critical determinant of malignant character. Here, we report that N-acetylgalactosaminyltransferase 2 (GALNT2), the enzyme that mediates the initial step of mucin type-O glycosylation, is a critical mediator of malignant character in hepatocellular carcinoma (HCC) that acts by modifying the activity of the epidermal growth factor receptor (EGFR). GALNT2 mRNA and protein were downregulated frequently in HCC tumors where these events were associated with vascular invasion and recurrence. Restoring GALNT2 expression in HCC cells suppressed EGF-induced cell growth, migration, and invasion in vitro and in vivo. Mechanistic investigations revealed that the status of the O-glycans attached to the EGFR was altered by GALNT2, changing EGFR responses after EGF binding. Inhibiting EGFR activity with erlotinib decreased the malignant characters caused by siRNA-mediated knockdown of GALNT2 in HCC cells, establishing the critical role of EGFR in mediating the effects of GALNT2 expression. Taken together, our results suggest that GALNT2 dysregulation contributes to the malignant behavior of HCC cells, and they provide novel insights into the significance of O-glycosylation in EGFR activity and HCC pathogenesis. Cancer Res; 71(23); 7270-9. Ó2011 AACR.

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Overexpression of MUC15 activates extracellular signal-regulated kinase 1/2 and promotes the oncogenic potential of human colon cancer cells

Cited by 48 publications

References 23 publications

Verification of Male Infertility Biomarkers in Seminal Plasma by Multiplex Selected Reaction Monitoring Assay

Verification of Male Infertility Biomarkers in Seminal Plasma by Multiplex Selected Reaction Monitoring Assay

The Tumor Microenvironment in Colorectal Carcinogenesis

Mucin Glycosylating Enzyme GALNT2 Regulates the Malignant Character of Hepatocellular Carcinoma by Modifying the EGF Receptor

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