Identification of SOCS2 and SOCS6 as biomarkers in human colorectal cancer

Letellier, Elisabeth; Schmitz, Martine; Baig, Komal; Beaume, Nicolas; Schwartz, Chantal; Frasquilho, Sónia; Antunes, Laurent; Marcon, Norman E.; Nazarov, Petr V.; Vallar, Laurent; Even, Jos; Haan, Serge

doi:10.1038/bjc.2014.377

Cited by 62 publications

(56 citation statements)

References 54 publications

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“…The environment may further regulate SOCS6, CRL5 or proteasome levels or activity, providing additional inputs to modulate the mode and speed of migration. This mechanism may be important in some cancers, where decreased SOCS6 expression has been associated with aggressive disease and increased metastasis (Fang et al, 2015; Letellier et al, 2014; Li et al, 2015; Wu et al, 2013; Zhu et al, 2013). …”

Section: Discussionmentioning

confidence: 99%

The ubiquitin-proteasome system regulates focal adhesions at the leading edge of migrating cells

Teckchandani

Cooper

2016

eLife

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Cell migration requires the cyclical assembly and disassembly of focal adhesions. Adhesion induces phosphorylation of focal adhesion proteins, including Cas (Crk-associated substrate/p130Cas/BCAR1). However, Cas phosphorylation stimulates adhesion turnover. This raises the question of how adhesion assembly occurs against opposition from phospho-Cas. Here we show that suppressor of cytokine signaling 6 (SOCS6) and Cullin 5, two components of the CRL5SOCS6 ubiquitin ligase, inhibit Cas-dependent focal adhesion turnover at the front but not rear of migrating epithelial cells. The front focal adhesions contain phospho-Cas which recruits SOCS6. If SOCS6 cannot access focal adhesions, or if cullins or the proteasome are inhibited, adhesion disassembly is stimulated. This suggests that the localized targeting of phospho-Cas within adhesions by CRL5SOCS6 and concurrent cullin and proteasome activity provide a negative feedback loop, ensuring that adhesion assembly predominates over disassembly at the leading edge. By this mechanism, ubiquitination provides a new level of spatio-temporal control over cell migration.DOI: http://dx.doi.org/10.7554/eLife.17440.001

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Section: Discussionmentioning

confidence: 99%

The ubiquitin-proteasome system regulates focal adhesions at the leading edge of migrating cells

Teckchandani

Cooper

2016

eLife

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“…Reduced expression of SOCS6 has been observed in many human cancers and its down-regulation is correlated with aggressive tumor progression and poor prognosis, suggesting the importance of SOCS6 in tumor growth and progression [25,26,27,28]. It was recently reported that the SOCS6 level is also reduced in CRC and may serve as a diagnostic biomarker for CRC patients [17]. This result is consistent with our findings that SOCS6 is a functional target of miR-301a.…”

Section: Discussionmentioning

confidence: 99%

MiR-301a Promotes Colorectal Cancer Cell Growth and Invasion by Directly Targeting SOCS6

Fang

Sun

Xiang

et al. 2015

Cell Physiol Biochem

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Background/Aims: Colorectal cancer (CRC) is one of the most common malignancies worldwide, and microRNAs play a crucial role in CRC biology. The purpose of this study was to investigate the exact functions and potential mechanisms of action of miR-301a in CRC. Methods: Quantitative real-time PCR was conducted to assess the expression of miR-301a. Cell proliferation was detected using MTT and colony formation assay, and cell invasion and migration were evaluated using Transwell assay. Luciferase reporter assay was used to identify the direct regulation of suppressor of cytokine signaling 6 (SOCS6) by miR-301a. Results: We first confirmed the upregulation of miR-301a in CRC tissues and cell lines. Gain-of-function and loss-of-function studies in the human CRC cell lines, SW480 and SW620, showed that miR-301a acts as an oncogene by increasing cell proliferation, migration and invasion as well as tumor growth. Furthermore, SOCS6 was identified as a target gene of miR-301a. Reintroduction of SOCS6 partially abrogated miR-301a-induced cell proliferation, migration and invasion. Conclusion: These data suggest that miR-301a promotes CRC progression by directly downregulating SOCS6 expression, and miR-301a may represent a novel biomarker for the prevention and treatment of CRC.

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“…SOCS2 expression is generally associated with increased body growth in rodents (9). Expression of SOCS2 is associated with positive prognosis in human breast cancer (23,24), but with malignancy in prostate (25) and colorectal (26) cancer. Its role in hematological malignancies is not yet clear, although SOCS2 is involved in T-cell differentiation (27), and stability (28).…”

Section: Localization Of Wnt1-inducible Signaling Pathway Protein 1mentioning

confidence: 99%

Differential Expression of Ccn4 and Other Genes Between Metastatic and Non-metastatic EL4 Mouse Lymphoma Cells

Chahal

Legaspi

et al. 2016

CGP

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EL4 is a murine lymphoma cell line developed in 1945 by treating C57 black mice with 9:10-dimethyl-1:2-benzanthracene (1). The cells were originally propagated in animal hosts, prior to adaptation to cell culture. EL4 cells were used for many years as a source of interleukin-2 (IL2), which they secrete when treated with phorbol 12-myristate 13-acetate (PMA).The EL4 cell line originally provided to us, by a colleague at the University of Washington, was heterogeneous with respect to PMA response. We, therefore, developed and characterized EL4 sub-lines. Wild-type (WT)-derived cell lines, which are PMA responsive, grow readily in suspension culture as did the original strain. Variant (V)-derived (PMA-resistant) sub-lines were selected for enhanced adhesion to tissue culture plastic (2). Clonal lines were developed from both cell types by limiting dilution (3). The PMA sensitivity of WT-derived cells, as reflected by PMA-induced IL2 production and mitogen-activated protein kinase (ERK1/2) activation, has been attributed to expression of Ras guanyl nucleotide releasing protein 1 (RasGRP1), which binds PMA and directly activates Ras (4); V-derived cells do not express RasGRP1.Clonal EL4 cell lines were used for experimental metastasis studies in syngeneic mice, with WT2 and V7 as prototypes (5, 6). WT2 cells do not form tumors (nonmetastatic), while V7 cells form liver tumors (metastatic) after tail vein injection. 'Metastasis' more strictly refers to tumorigenesis in this model, since circulating EL4 cells home to the liver to form tumors (5). The clonal C5 cell line was developed after stably overexpressing human hemagllutinin (HA)-tagged phospholipase D2 (PLD2) in V7 cells in order to characterize the signaling role of PLD2 using a cell line expressing little or no endogenous PLD2 (5). As compared to V7, C5 cells exhibit increased cell migration (7) and tumor growth (5), providing an early example of the positive role of PLD2 in tumorigenesis.This report presents data from microarray analyses comparing transcripts expressed by these three EL4 cell types, with the goal of further defining their phenotypes.

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Identification of SOCS2 and SOCS6 as biomarkers in human colorectal cancer

Cited by 62 publications

References 54 publications

The ubiquitin-proteasome system regulates focal adhesions at the leading edge of migrating cells

The ubiquitin-proteasome system regulates focal adhesions at the leading edge of migrating cells

MiR-301a Promotes Colorectal Cancer Cell Growth and Invasion by Directly Targeting SOCS6

Differential Expression of Ccn4 and Other Genes Between Metastatic and Non-metastatic EL4 Mouse Lymphoma Cells

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