Identification of TRAK1 (Trafficking protein, kinesin-binding 1) as MGb2-Ag: A novel cancer biomarker

Zhang, Faming; Ren, Gui; Lu, Yuanyuan; Jin, Bin; Wang, Jun; Chen, Xiong; Liu, Zhenxiong; Li, Kai; Nie, Yongzhan; Wang, Xin; Fan, Daiming

doi:10.1016/j.canlet.2008.09.031

Cited by 23 publications

(20 citation statements)

References 30 publications

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“…5A). When we scored these 110 sections based on a scoring system reported by Zhang et al (31), 100% of the controls ( n = 10) received a score of 1+ or less, which meant that CPN was weakly or not expressed in controls. However, across all stages of breast cancer represented on the array, 85% of the samples received scores higher than 1+, and 70% received scores higher than 2+ (Fig.…”

Section: Resultsmentioning

confidence: 99%

Circulating Proteolytic Products of Carboxypeptidase N for Early Detection of Breast Cancer

Chen

et al. 2014

Clinical Chemistry

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Background Carboxypeptidase N (CPN) plays an important role in regulating vasoactive peptide hormones, growth factors, and cytokines by specifically cleaving their C-terminal basic residues. Herein we demonstrated that the circulating peptides specifically cleaved by CPN in the tumor microenvironment can indeed be stage-specific indicators of breast cancer. Methods The activity of CPN was evaluated using an ex-vivo peptide cleavage assay, in which synthesized C3f peptide (His6-C3f_S1304-R1320-His6) is incubated in interstitial fluids of breast tumor and adjacent normal breast tissues in mice with orthotopic implantation of the human cell line MDA-MB-231. Fragment profiling, by an approach combining nanopore fractionation and mass spectrometry, revealed the nature and extent of cleavage by CPN. These results correlated with the level of CPN-catalyzed peptides in blood specimens taken from the tumor-bearing mice, healthy women and breast cancer patients. CPN expression in the same set of samples was further examined by immunohistochemistry and immunoblotting. Results We showed that generation of C3f_R1310-L1319 specifically correlated with the CPN expression level. In both the mouse and clinical patient samples, the amount of CPN was clearly increased in tumor tissues compared to that seen in normal breast tissue, while its counterpart in blood remained constant. The amount of 6 CPN-catalyzed peptides predominantly increased in sera taken from the mice (n=8) at 2 weeks after orthotropic implantation. Six homologous peptides displayed the significantly higher expression in the patients’ plasma as early as the first pathologic stage of breast cancer. Conclusions The amount of circulating CPN-catalyzed peptides reported here reflects the extent of this enzyme’s activity in tumors, and our results clearly indicate their strong potential as biomarkers for non-invasive and early diagnosis of breast cancer.

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Section: Resultsmentioning

confidence: 99%

Circulating Proteolytic Products of Carboxypeptidase N for Early Detection of Breast Cancer

Chen

et al. 2014

Clinical Chemistry

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“…TRAK1 has been shown to play a role in endosome-to-lysosome trafficking and GABA(A) receptor homeostasis in hypertonia, which is observed in human neurological diseases [30, 31]. TRAK1 has been shown to be a promising diagnostic marker for gastric cancer [32] and a prognostic marker in colorectal cancer [33]. In the present study, we have found that TRAK1 was co-regulated with DAPK1 and was a favorable prognostic marker in bladder cancer.…”

Section: Discussionmentioning

confidence: 99%

The prognostic significance of DAPK1 in bladder cancer

et al. 2017

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Bladder cancer is one of the leading causes of cancer-related death in men, however, there was only limited effective treatment for invasive bladder cancer. DAPK1 has been shown to play important role in apoptosis and autophagy to suppress cancer progression. Previous results have shown that DAPK1 promoter was hypermethylated in the majority of bladder cancer specimens, however, the prognostic significance of DAPK1 in bladder cancer has yet to be demonstrated. In the present study, we found that DAPK1 expression was negatively associated with tumor stage and a low level expression of DAPK1 in bladder cancer specimens were associated with shorter survival in bladder cancer patients in 3 independent bladder cancer datasets (n = 462). Further investigation showed that FGFR3 knockdown resulted in downregulation of DAPK1 in bladder cancer cell line, suggesting that FGFR3 may be an upstream factor of DAPK1. Further analysis of the 3 independent bladder cancer datasets have identified ACOX1, UPK2, TRAK1, PLEKHG6 and MT1X genes had their expression significantly correlated with that of DAPK1. Knockdown of DAPK1 in bladder cancer T24 cells resulted in downregulation of ACOX1, UPK2 and TRAK1. Interestingly, TRAK1, by itself, was a favorable prognostic marker in the 3 independent bladder cancer datasets. Importantly, by using connectivity mapping with DAPK1-associated gene signature, we found that vemurafenib and trametinib could possibly reverse DAPK1-associated gene signature, suggesting that inhibition of Raf/MEK pathway may be a potential therapeutic approach for bladder cancer. Indeed, treatment of vemurafenib in T24 bladder cancer cells resulted in upregulation of DAPK1 confirming our connectivity mapping, while knockdown of DAPK1 resulted in reduced sensitivity towards inhibition of Braf signaling by vemurafenib. Together, our results suggest that DAPK1 is an important prognostic marker and therapeutic target for bladder cancer and have identified possible therapeutic agents for future testing in bladder cancer models with low DAPK1 expression.

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“…We investigated for the presence of Helicobacter pylori. The nuclear proliferation antigen Ki-67 (mouse anti-Ki-67 monoclonal antibody [mAb], 1:100 dilution, Santa, Barbara, CA), the gastrointestinal cancer-associated antigen TRAK1 (MGb2-Ag) [2] (mouse anti-TRAK1/Mgb2-Ag mAb, 1:300), synaptophysin (rabbit anti-synaptophysin mAb, 1:100; Dako, Barbara, CA), and neurofilament [3,4] (mouse anti-neurofilament mAb, 1:100, Dako, Barbara, CA) were used to precisely define the mucosa and neuronal and ganglion cell components.…”

Section: Case Reportmentioning

confidence: 99%

“…Meckel's diverticulum (MD) is the most common congenital anomaly of the gastrointestinal tract and is located in the distal ileum [1]; it occurs in 2-3% of the population [2]. It is a true diverticulum as it is composed of all 3 layers of the intestinal wall [3] and, in approximately 50% of cases contains ectopic tissue.…”

Section: Introductionmentioning

confidence: 99%

Pathological feature of a giant ileal Meckel’s diverticulum with ectopic gastric mucosa

Wang

Dhawan

Lin

et al. 2010

Clin J Gastroenterol

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The ileum generally works well, whereas Meckel's diverticulum (MD) has complications including bleeding, obstruction, intussusception, diverticulitis, and perforation. Our knowledge of the pathological features of the MD muscular layer and mucosa is limited. We report a rare case of giant MD that was diagnosed by double-balloon enteroscopy (DBE). The pathological features of the mucosa were evaluated by investigation for Helicobacter pylori; and the nuclear proliferation antigen Ki-67, the gastrointestinal cancer-associated biomarker TRAK1, synaptophysin, and neurofilament were used to precisely define the mucosa and neuronal and ganglion cell components. The pathophysiology of MD is discussed and a literature review is presented. We believe that this is the first report of a systematic histochemical analysis of the mucosa and myenteric plexus of MD and the normal ileum. The present investigation may provide novel evidence of pathological abnormalities resulting in the complex complications of MD.

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Identification of TRAK1 (Trafficking protein, kinesin-binding 1) as MGb2-Ag: A novel cancer biomarker

Cited by 23 publications

References 30 publications

Circulating Proteolytic Products of Carboxypeptidase N for Early Detection of Breast Cancer

Circulating Proteolytic Products of Carboxypeptidase N for Early Detection of Breast Cancer

The prognostic significance of DAPK1 in bladder cancer

Pathological feature of a giant ileal Meckel’s diverticulum with ectopic gastric mucosa

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