Prognostic impact of Metadherin–SND1 interaction in colon cancer

Wang, Nan; Du, Xin; Zang, Li; Song, Nan; Yang, Tao; Dong, Rui; Wu, Tao; He, Xianli; Lu, Jianguo

doi:10.1007/s11033-012-1933-0

Cited by 43 publications

(32 citation statements)

References 27 publications

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“…In human colon cancer, SND1 is upregulated and contributes to cancer development at the early stages via activation of the Wnt signaling pathway (33). Meanwhile, SND1 could also interact with AEG-1 in colon cancer (29). In the present study, we demonstrate that SND1 plays important roles in breast cancer metastasis.…”

Section: Discussionsupporting

confidence: 56%

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SND1 Acts Downstream of TGFβ1 and Upstream of Smurf1 to Promote Breast Cancer Metastasis

Liu

Cui

et al. 2015

Cancer Research

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SND1 is an AEG-1/MTDH/LYRIC-binding protein that is upregulated in numerous human cancers, where it has been assigned multiple functional roles. In this study, we report its association with the TGFb1 signaling pathway, which promotes epithelial-mesenchymal transition (EMT) in breast cancer. SND1 was upregulated in breast cancer tissues, in particular in primary invasive ductal carcinomas. Transcriptional activation of the SND1 gene was controlled by the TGFb1/Smad pathway, specifically by activation of the Smad2/Smad3 complex. The SND1 promoter region contained several Smad-specific recognition domains (RD motifs), which were recognized and bound by the Smad complex that enhanced the transcriptional activation of SND1. We found that SND1 promoted expression of the E3 ubiquitin ligase Smurf1, leading to RhoA ubiquitination and degradation. RhoA degradation in breast cancer cells disrupted F-actin cytoskeletal organization, reduced cell adhesion, increased cell migration and invasion, and promoted metastasis. Overall, our results define a novel role for SND1 in regulating breast tumorigenesis and metastasis. Cancer Res; 75(7); 1275-86. Ó2015 AACR.

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Section: Discussionsupporting

confidence: 56%

“…SND1 upregulation has been reported in various malignant tumors, such as hepatocellular carcinoma (27), prostate cancer (28), and colon cancer (29). The molecular mechanisms for the involvement of SND1 in tumorigenesis of different types of cancers appear to be diverse.…”

Section: Discussionmentioning

confidence: 99%

SND1 Acts Downstream of TGFβ1 and Upstream of Smurf1 to Promote Breast Cancer Metastasis

Liu

Cui

et al. 2015

Cancer Research

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“…However, other studies analysing the AEG-1 expression in CRC showed no or only slight nuclear expression (214,247,310,311). The differences in AEG-1 localisation between our study and the other studies performed in CRC, might be due to different antibodies and staining The AEG-1 expression did not differ between the distant normal mucosa and the adjacent mucosa, neither in the cytoplasm nor in the nucleus, and was therefore considered as one group for further analyses to increase the sample size.…”

Section: Resultsmentioning

confidence: 92%

“…The determination of these elements and the impact of mutations is very challenging. We also analysed the corresponding normal mucosa, whenever available, to be able to identify (214,247,310,311).…”

Section: Resultsmentioning

confidence: 99%

Astrocyte elevated gene-1 in relation to colorectal cancer development and radiotherapy response

Gnosa¹

2015

Linköping University Medical Dissertations

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“…85 Immunohistochemical staining of samples from human colon cancer and their corresponding non-cancerous colon tissues revealed simultaneous increase of expression of AEG-1 and TSN in tumor samples compared with paired non-cancerous colon tissues. 77 Importantly, their positive expression was both significantly associated with nodal status, pathological stage and differentiation. Moreover, the overall survival rate in colon cancer patients with positive expression of both AEG-1 and TSN was significantly reduced proposing the co-expression of AEG-1 and TSN as a potent marker for prediction of the prognosis in colon cancer.…”

Section: Role Of Tsn In Carcinogenesis and Cell Deathmentioning

confidence: 98%

Tudor staphylococcal nuclease: biochemistry and functions

et al. 2016

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Tudor staphylococcal nuclease (TSN, also known as Tudor-SN, SND1 or p100) is an evolutionarily conserved protein with invariant domain composition, represented by tandem repeat of staphylococcal nuclease domains and a tudor domain. Conservation along significant evolutionary distance, from protozoa to plants and animals, suggests important physiological functions for TSN. It is known that TSN is critically involved in virtually all pathways of gene expression, ranging from transcription to RNA silencing. Owing to its high protein-protein binding affinity coexistent with enzymatic activity, TSN can exert its biochemical function by acting as both a scaffolding molecule of large multiprotein complexes and/or as a nuclease. TSN is indispensible for normal development and stress resistance, whereas its increased expression is closely associated with various types of cancer. Thus, TSN is an attractive target for anti-cancer therapy and a potent tumor marker. Considering ever increasing interest to further understand a multitude of TSN-mediated processes and a mechanistic role of TSN in these processes, here we took an attempt to summarize and update the available information about this intriguing multifunctional protein. TSN is an evolutionarily conserved protein having a pivotal role in the regulation of gene expression. TSN acts both as a scaffolding protein and as a nuclease. TSN sustains cell viability and its cleavage by proteases facilitates cell death. TSN is implicated in key cancer-related processes and is a potent marker of various types of tumors. Open questions:How is nucleolytic activity of TSN regulated in vivo and how this affects interaction of TSN with downstream targets? What are the structural bases and functional consequences of distinct intracellular localization patterns of TSN in animals and plants? What are the molecular mechanisms of the TSN-mediated cancerogenesis?God has given you one face, and you make yourself another (William Shakespeare). Being true for all living organisms, accurate spatio-temporal regulation of gene expression is a fundamental mechanism underlying development, homeostasis and adaptation to the environment. Eukaryotic gene expression is a cumulative outcome of a multitude of molecular processes, including transcription, mRNA splicing, stability and translation, chromatin modification, as well as protein stability and modification. Each of these processes is in turn controlled by a highly dedicated repertoire of proteins. However, one protein, Tudor staphylococcal nuclease (TSN, also known as Tudor-SN, SND1 or p100) appears to act in most of the gene expression pathways.TSN is an evolutionarily conserved protein found in all eukaryotic lineages, except budding yeast, Saccharomyces cerevisiae. Conservation along significant evolutionary distance suggests important physiological functions for TSN. Invariant domain composition of TSN comprises tandem repeat of four staphylococcal nuclease (SN)-like domains (hereafter referred to as SN domains) at the N terminus and a fusio...

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Prognostic impact of Metadherin–SND1 interaction in colon cancer

Cited by 43 publications

References 27 publications

SND1 Acts Downstream of TGFβ1 and Upstream of Smurf1 to Promote Breast Cancer Metastasis

SND1 Acts Downstream of TGFβ1 and Upstream of Smurf1 to Promote Breast Cancer Metastasis

Astrocyte elevated gene-1 in relation to colorectal cancer development and radiotherapy response

Tudor staphylococcal nuclease: biochemistry and functions

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