Suppressor of cytokine signaling 1 modulates invasion and metastatic potential of colorectal cancer cells

David, Muriel D.; Naudin, Cécile; Letourneur, Martine; Polrot, Mélanie; Renoir, Jack‐Michel; Lazar, Vladimir; Dessen, Philippe; Roche, Serge; Bertoglio, Jacques; Pierre, Josiane

doi:10.1016/j.molonc.2014.03.014

Cited by 30 publications

(28 citation statements)

References 51 publications

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“…29 Overexpression of SOCS1 increased the mir-200 family of miRNAs, which promotes the mesenchymal-epithelial transition and reduces tumor migration in colon cancer cells. 30 These studies demonstrated the crucial role of sfrp1, dkk3, Figure 3. FFAR2 deficiency changed histone modification on inflammation regulators.…”

Section: Discussionmentioning

confidence: 85%

Loss of FFAR2 promotes colon cancer by epigenetic dysregulation of inflammation suppressors

Pan

Oshima²,

Huang

et al. 2018

Intl Journal of Cancer

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Free fatty acid receptor 2 (FFAR2, also named GPR43), is activated by short-chain fatty acids (SCFAs), such as butyrate, that are produced when gut bacteria ferment dietary fiber. FFAR2 has been suggested to regulate colonic inflammation, which is a major risk factor for the development of colon cancer and is also linked to epigenetic dysregulation in colon carcinogenesis. The current study assessed whether FFAR2, acting as an epigenetic regulator, protects against colon carcinogenesis. To mimic the mild inflammation that promotes human colon cancer, we treated mice with dextran sodium sulfate (DSS) overnight, which avoids excessive inflammation but induces mild inflammation that promotes colon carcinogenesis in the Apc and the azoxymethane (AOM)-treated mice. Our results showed that FFAR2 deficiency promotes the development of colon adenoma in the Apc /DSS mice and the progression of adenoma to adenocarcinoma in the AOM/DSS mice. FFAR2's downstream cAMP-PKA-CREB pathway was enhanced, leading to overexpression of histone deacetylases (HDACs) in the FFAR2-deficient mice. ChIP-qPCR analysis revealed differential binding of H3K27me3 and H3K4me3 histone marks onto the promoter regions of inflammation suppressors (e.g., sfrp1, dkk3, socs1), resulting in decreased expression of these genes in the FFAR2-deficient mice. Also, more neutrophils infiltrated into tumors and colon lamina propria of the FFAR2-deficient mice. Depletion of neutrophils blocked the progression of colon tumors. In addition, FFAR2 is required for butyrate to suppress HDAC expression and hypermethylation of inflammation suppressors. Therefore, our results suggest that FFAR2 is an epigenetic tumor suppressor that acts at multiple stages of colon carcinogenesis.

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Section: Discussionmentioning

confidence: 85%

Loss of FFAR2 promotes colon cancer by epigenetic dysregulation of inflammation suppressors

Pan

Oshima²,

Huang

et al. 2018

Intl Journal of Cancer

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“…Their findings are somewhat contradictory. In the David et al study, the highest SOCS1 mRNA and protein levels were seen in normal colon and early-stage adenomas, whereas the lowest levels were detected in advanced and poorly differentiated carcinomas 22 . Nonetheless, high SOCS1 protein level was still noted in 63% of advanced stage IV CRC tumours.…”

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confidence: 85%

“…Notably, CIMP colorectal tumours are associated with specific genetic features and poor clinical outcomes 20 21 , but SOCS1 methylation in CIMP CRCs has been linked to better overall patient survival than those without 18 . Only two recently published studies have so far probed the abundance of SOCS1 mRNA or protein in relatively small cohorts of human CRC samples 22 23 . Their findings are somewhat contradictory.…”

mentioning

confidence: 99%

“…While mice with Socs1 deletion in all tissues, except T and B cells, spontaneously developed colon inflammation and tumours 24 , its silencing in antigen-presenting macrophages and dendritic cells fostered anti-tumour immunity 25 26 . The role of SOCS1 in CRC cells has so far been investigated in a single published study by David et al 22 . The authors concluded that SOCS1 works as a suppressor of metastasis, on the basis that its overexpression in human SW620 CRC cells reduced morphological transformation, invasion and metastasis without affecting proliferation, anchorage-independent growth or tumourigenesis 22 .…”

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confidence: 99%

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Tumour-promoting role of SOCS1 in colorectal cancer cells

Tobelaim

Beaurivage

Champagne

et al. 2015

Sci Rep

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The SOCS1 (Suppressor Of Cytokine Signalling 1) protein is considered a tumour suppressor. Notably, the SOCS1 gene is frequently silenced in cancer by hypermethylation of its promoter. Besides blocking inflammation, SOCS1 tumour suppressor activity involves Met receptor inhibition and enhancement of p53 tumour suppressor activity. However, the role of SOCS1 in colorectal cancer (CRC) remains understudied and controversial. Here, we investigated SOCS1 relevance for CRC by querying gene expression datasets of human CRC specimens from The Cancer Genome Atlas (TCGA), and by SOCS1 gain/loss-of-function analyses in murine and human colon carcinoma cells. Our results show that SOCS1 mRNA levels in tumours were more often elevated than reduced with respect to matched adjacent normal tissue of CRC specimens (n = 41). The analysis of TCGA dataset of 431 CRC patients revealed no correlation between SOCS1 expression and overall survival. Overexpression of SOCS1 in CRC cells triggered cell growth enhancement, anchorage-independent growth and resistance to death stimuli, whereas knockdown of SOCS1 reduced these oncogenic features. Moreover, SOCS1 overexpression in mouse CT26 cells increased tumourigenesis in vivo. Biochemical analyses showed that SOCS1 pro-oncogenic activity correlated with the down-modulation of STAT1 expression. Collectively, these results suggest that SOCS1 may work as an oncogene in CRC.

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“…What's more, SOCS1 and JAK2/STAT3 pathway are discussed in hepatocellular carcinoma [24]. David et al uncover that the overexpression of SOCS1 give rises to cell morphology changes and obviously reduced tumor cell invasion in vitro [25]. In this study, the results of recuse assays demonstrates that JAK2/STAT3 signaling pathway inactivation caused by GATA6-AS1 overexpression, is reversed by silencing of SOCS1 and Colivelin.…”

Section: Discussionmentioning

confidence: 52%

Long Non-Coding RNA GATA6-AS1 Inhibits Proliferation and Promotes Apoptosis of Lung Adenocarcinoma Through Sponging miR-331-3p and Regulating SOCS1/JAK2/STAT3 Pathway

Huo

Wang

Jiang

et al. 2020

Preprint

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Abstract Background: Accumulating evidence has indicated the remarkable roles of long non-coding RNAs (lncRNAs) as oncogenes or tumor suppressors in many malignancies. The involvement of lncRNA GATA6-AS1 in cancers remains largely undiscovered. Herein, our research was aimed at elucidating the function and mechanism of GATA6-AS1 in lung adenocarcinoma (LUAD).Methods: Gene expression was measured through qRT-PCR and WB. Cell proliferation ratio was determined using CCK-8 and EdU assays. Cell apoptosis ratio was determined using TUNEL and flow cytometry assays. Molecular interactions were examined through RIP, RNA pull-down and luciferase reporter assays.Results: GATA6-AS1 expression was markedly down-regulated in LUAD cell lines. GATA6-AS1 could inhibit LUAD cell proliferation and promote cell apoptosis. Mechanistically, GATA6-AS1 was identified as the molecular sponge for miR-331-3p, whose knockdown in LUAD cells could reinforce the tumor-suppressing effects of GATA6-AS1 overexpression. Moreover, GATA6-AS1 functions as a competing endogenous RNA (ceRNA) through sequestering miR-331-3p to deregulate SOCS1, thus inhibiting JAK2/STAT3 signaling pathway and suppressing LUAD cell viability.Conclusions: These results demonstrate the tumor-suppressing function and mechanism of lncRNA GATA6-AS1 in LUAD cells. The axis of GATA6-AS1/miR-331-3p/SOCS1/JAK2/STAT3 can be adopted as a novel approach for LUAD treatment.

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Suppressor of cytokine signaling 1 modulates invasion and metastatic potential of colorectal cancer cells

Cited by 30 publications

References 51 publications

Loss of FFAR2 promotes colon cancer by epigenetic dysregulation of inflammation suppressors

Loss of FFAR2 promotes colon cancer by epigenetic dysregulation of inflammation suppressors

Tumour-promoting role of SOCS1 in colorectal cancer cells

Long Non-Coding RNA GATA6-AS1 Inhibits Proliferation and Promotes Apoptosis of Lung Adenocarcinoma Through Sponging miR-331-3p and Regulating SOCS1/JAK2/STAT3 Pathway

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