Suppression of human selenium‐binding protein 1 is a late event in colorectal carcinogenesis and is associated with poor survival

Kim, Hyunki; Kang, Hyun Ju; You, Kwon Tae; Kim, Se Hoon; Lee, Kang Young; Kim, Tae Il; Kim, Chul; Song, Si Young; Kim, Hye Jung; Lee, Cheolju; Kim, Hoguen

doi:10.1002/pmic.200500629

Cited by 99 publications

(113 citation statements)

References 17 publications

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“…A number of these proteins could be predicted to play roles in tumorigenesis or tumor growth. Some of the identified proteins have been shown to be differentially expressed in experimental models or other tumor types such as colon or liver cancer ( [15,16,25,26]). Overall the proteins found to be over-expressed or under-expressed in tumoral tissue fell into the categories shown in Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Many of these proteins were involved in cellular metabolism while a number were cytoskeletal proteins. Several of these proteins have also been reported to be differentially expressed in either hepatocellular carcinoma or other tumor types, for example alcohol dehydrogenase and aldehyde dehydrogenase [12], carbamyl phosphate synthase [13], selenium binding protein 1 and DNA helicase RuvB-like protein 2 ( [14][15][16]). …”

Section: Proteins Under-expressed In the Tumoral Liver Tissue Comparementioning

confidence: 99%

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Proteomic Analysis of Differentially Expressed Proteins in Peripheral Cholangiocarcinoma

Darby

Vuillier-Devillers

Pinault

et al. 2010

Cancer Microenvironment

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Cholangiocarcinoma is an adenocarcinoma of the liver which has increased in incidence over the last thirty years to reach similar levels to other liver cancers. Diagnosis of this disease is usually late and prognosis is poor, therefore it is of great importance to identify novel candidate markers and potential early indicators of this disease as well as molecules that may be potential therapeutic targets. We have used a proteomic approach to identify differentially expressed proteins in peripheral cholangiocarcinoma cases and compared expression with paired non-tumoral liver tissue from the same patients. Two-dimensional fluorescence difference gel electrophoresis after labeling of the proteins with cyanines 3 and 5 was used to identify differentially expressed proteins. Overall, of the approximately 2,400 protein spots visualised in each gel, 172 protein spots showed significant differences in expression level between tumoral and non-tumoral tissue with p<0.01. Of these, 100 spots corresponding to 138 different proteins were identified by mass spectrometry: 70 proteins were over-expressed whereas 68 proteins were under-expressed in tumoral samples compared to nontumoral samples. Among the over-expressed proteins, immunohistochemistry studies confirmed an increased expression of 14-3-3 protein in tumoral cells while α-smooth muscle actin and periostin were shown to be overexpressed in the stromal myofibroblasts surrounding tumoral cells. α-Smooth muscle actin is a marker of myofibroblast differentiation and has been found to be a Ian A. Darby, Karine Vuillier-Devillers, and Émilie Pinault have equally contributed to this work.

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Section: Discussionmentioning

confidence: 99%

Section: Proteins Under-expressed In the Tumoral Liver Tissue Comparementioning

confidence: 99%

Proteomic Analysis of Differentially Expressed Proteins in Peripheral Cholangiocarcinoma

Darby

Vuillier-Devillers

Pinault

et al. 2010

Cancer Microenvironment

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“…There is relatively little information on Selenium-Binding Protein 1 (SELENBP1) which was originally identified from mouse liver [15] and subsequently cloned from human liver [16]. Interestingly, SELENBP1 may have an important role in cancer because significantly decreased SELENBP1 mRNA expression was observed in ovarian cancer [17] as well as colorectal [18], prostate [19], lung [20], gastrointestinal [21] and papillary thyroid cancer [22] by proteomic and differential array analysis. Decreased expression of SELENBP1 was associated with poorer survival of patients diagnosed with poorly differentiated lung tumors [20].…”

Section: Introductionmentioning

confidence: 99%

Selenium-Binding Protein 1 expression in ovaries and ovarian tumors in the laying hen, a spontaneous model of human ovarian cancer

Stammer

Edassery

Barua

et al. 2008

Gynecologic Oncology

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Objective-Reduced Selenium-Binding Protein 1 (SELENBP1) expression was recently shown in multiple cancers. There is little information on the expression and function of SELENBP1 in cancer progression. In order to develop a better understanding of the role of SELENBP1 in ovarian cancer, our objective was to determine if SELENBP1 is expressed in the normal ovaries and ovarian tumors in the egg-laying hen, a spontaneous model of human ovarian cancer.Methods-SPB1 mRNA expression in normal ovary (n=20) and ovarian tumors (n=23) was evaluated by RT-PCR. Relative levels of mRNA were compared by quantitative RT-PCR (qRT-PCR) in selected samples. SELENBP1 protein expression was evaluated by 1D Western Blot and immunohistochemistry with a commercial anti-human SELENBP1 antibody.Results-SELENBP1 mRNA and protein was expressed in 100% of normal and ovarian tumors and qRT-PCR confirmed decreased mRNA expression in 80% of ovarian tumors. SELENBP1 was primarily localized in surface epithelial cells of normal ovaries. In ovaries containing early tumor lesions, SELENBP1 expression was reduced in the surface epithelium near the tumor and was expressed in tumor cells, while more distant regions with normal histology retained SELENBP1 expression in the surface epithelium.Conclusions-We have shown for the first time that SELENBP1 is expressed in both normal ovaries and ovarian tumors in the hen and that SELENBP1 expression is altered in the vicinity of the tumor. Furthermore, SELENBP1 expression in normal ovarian surface epithelium and in ovarian tumors parallels that previously reported for ovarian cancer in women.

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“…Or, the authors hypothesize that the ETC-1922159 drug is not effective on wild type SELENBP1 and thus the observed data on SELENBP1 might need further testing. This is due to the fact that suppression of SELENBP1 has been found to be a late event in colorectal cancer 223 . However, when we look across the ranking of the other tables the ranking of SELENBP1 has been found to be associated with a very high ranking on majority basis and this points to the fact that SELENBP1 should be up regulated to suppress the cancer cells as it is anticarcionogenic in nature and the effect of ETC-1922159 on SELENBP1 is not that potent.…”

Section: Preprints (Wwwpreprintsorg) | Not Peer-reviewed | Postedmentioning

confidence: 99%

Revealing ETC-1922159 Affected Unknown 3<em><sup>rd</sup></em> order WNT10B-X-X Combinations, in Silico

Sinha¹

2017

Preprint

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WNT10B belongs to the family of WNT proteins that are implicated in a range of phenomena that are affected by the Wnt signaling pathway. Recent studies have shown that WNT10B plays a role in colorectal cancer. WNTs have been found to directly affect the stemness of the tumor cells via regulation of ASCL2. Switching off the ASCL2 literally blocks the stemness process of the tumor cells and vice versa. Furthermore, recent findings suggest BVES to be highly suppressed in malignancies and in vitro deletions of BVES show higher Wnt signaling activity to induce stemness. WNT10B was found to be highly expressed in such cases. Often, in biology, we are faced with the problem of exploring relevant unknown biological hypotheses in the form of myriads of combination of factors that might be affecting the pathway under certain conditions. For example, WNT10B-ASCL2 is one such 2 nd order combination whose relation needs to be tested under the influence of recently developed porcupine-WNT inhibitor ETC-1922159. The inhibitor is known to suppress PORCN (porcupine) and thus inhibit a range of oncogenes known to be directly or indirectly affected by the Wnts. In a recent unpublished work in bioRxiv, Sinha 1 , we had the opportunity to rank these unknown biological hypotheses for down regulated genes at 2 nd order level after the drug was administered. The in silico observations showed that the combination of WNT10B-ASCL2 was assigned a relatively lower rank, thus validating the pipeline's efficacy with the confirmed wet lab experiment that indicate that both WNT10B and ASCL2 were down regulated after treatment in cancer cells. Here, we take one step further by in silico analysis of the 3 rd order combinations of WNT10B-X-X (X can be known or unknown factor), from a range of 100 randomly picked down regulated genes after ETC-1922159 treatment. The pipeline uses the density based HSIC (Hilbert Schmidt Information Criterion) sensitivity index with an rbf (radial basis function) kernel, which is known to be highly effective in sensitivity analysis. Various unknown/unexplored/untested 3 rd order biological hypotheses emerge some of which are confirmed in wet lab, while others need to be tested. The potential of such ranking is indispensable in the current era of search in a vast combinatorial forest. KEYWORDS -WNT pathway; porcupine inhibitor ETC-1922159; sensitivity analysis; colorectal cancer; unknown biological hypotheses; combinatorial search space; support vector ranking Conference, from 6-11 August 2017, held Significance WNT10B belongs to the family of WNT proteins that are implicated in a range of phenomena that are affected by the Wnt signaling pathway. Recent studies have shown that WNT10B plays a role in colorectal cancer. Often, we are faced with the problem of exploring relevant unknown biological hypotheses in the form of myriads of combination of factors that might be involved in the pathway. The current work reveals at in silico level, the 3rd order WNT10B associated combinations that might be affected by the admin...

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Suppression of human selenium‐binding protein 1 is a late event in colorectal carcinogenesis and is associated with poor survival

Cited by 99 publications

References 17 publications

Proteomic Analysis of Differentially Expressed Proteins in Peripheral Cholangiocarcinoma

Proteomic Analysis of Differentially Expressed Proteins in Peripheral Cholangiocarcinoma

Selenium-Binding Protein 1 expression in ovaries and ovarian tumors in the laying hen, a spontaneous model of human ovarian cancer

Revealing ETC-1922159 Affected Unknown 3<em><sup>rd</sup></em> order WNT10B-X-X Combinations, in Silico

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