Cancer-induced inflammation and inflammation-induced cancer in colon: a role for S1P lyase

Schwiebs, Anja; Juan, Martina Herrero San; Schmidt, Karl‐Hermann; Wiercinska, Eliza; Anlauf, Martin; Ottenlinger, Florian; Thomas, Dominique; Elwakeel, Eiman; Weigert, Andreas; Farin, Henner F.; Bönig, Halvard; Scholich, Klaus; Geißlinger, Gerd; Pfeilschifter, Josef; Radeke, Heinfried H.

doi:10.1038/s41388-019-0758-x

Cited by 31 publications

(32 citation statements)

References 58 publications

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“…Sphingolipid metabolites, including ceramide, sphingosine and S1P, have emerged as bioactive signaling molecules that regulate cell movement, differentiation, survival, inflammation, angiogenesis, calcium homeostasis and immunity [ 14 ]. Ceramide is considered to be responsible for antiproliferative responses, such as the inhibition of cell growth and induction of apoptosis, while S1P has opposite functions, including the promotion of cancer cell growth and angiogenesis, based on the sphingosine rheostat or ceramide-S1P rheostat theory [ 8 , 12 , 15 , 16 ]. In line with the sphingolipid rheostat theory, previous reports showed that SGPL1 was downregulated in colon cancer, leading to S1P accumulation in neoplastic intestinal tissues [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

Heterogenous Nuclear Ribonucleoprotein H1 Promotes Colorectal Cancer Progression through the Stabilization of mRNA of Sphingosine-1-Phosphate Lyase 1

Takahashi

Fujiya

Konishi

et al. 2020

IJMS

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The oncogenic properties of heterogeneous nuclear ribonucleoprotein H1 (hnRNP H1) have been reported, although the tumor-promoting mechanism remains unclear. We herein report the mechanism underlying colorectal cancer cell progression mediated by hnRNP H1. The growth of colorectal cancer cells was suppressed by hnRNP H1 downregulation. A terminal deoxynucleotidyl transferase dUTP nick-end labeling assay revealed the anti-apoptotic effect of hnRNP H1 in colorectal cancer cells. An RNA immunoprecipitation assay revealed that hnRNP H1 bound to sphingosine-1-phosphate lyase 1 (SGPL1). Reverse transcription-polymerase chain reaction revealed the high expression of hnRNP H1 mRNA in colorectal cancer cells and Spearman’s rank correlation coefficient showed a strong positive correlation between hnRNP H1 mRNA and SGPL1 mRNA. An siRNA of hnRNP H1 decreased SGPL1 mRNA expression in colorectal cancer cells, but not in non-tumorous cells. These findings suggested that hnRNP H1 increased SGPL1 mRNA expression specifically in cancer cells through direct binding. Targeted knockdown of hnRNP H1 or SGPL1 with siRNAs upregulated p53 phosphorylation and p53-associated molecules, resulting in cell growth inhibition, while hnRNP H1 upregulated the mRNA of SGPL1 and inhibited p53 activation, thereby promoting tumor cell growth. This is a novel mechanism underlying colorectal cancer cell progression mediated by hnRNP H1–SGPL1 mRNA stabilization.

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Section: Discussionmentioning

confidence: 99%

Heterogenous Nuclear Ribonucleoprotein H1 Promotes Colorectal Cancer Progression through the Stabilization of mRNA of Sphingosine-1-Phosphate Lyase 1

Takahashi

Fujiya

Konishi

et al. 2020

IJMS

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“…1b). Several studies have shown that SGPL1 knockout or knockdown in in vivo models of colorectal cancer supported transformation of normal colon epithelium into cancer cells Oskouian et al, 2006;Schwiebs et al, 2019; Fig 4 SGPL1 Sirna treatment increases cell adhesion. (a) Representative pictures of Western blot analysis of SGPL1 and E-cadherin protein expression in DLD-1 cells transfected with SGPL1 or scramble siRNA for 96 h (n = 5).…”

Section: Discussionmentioning

confidence: 99%

S1P Lyase siRNA Dampens Malignancy of DLD‐1 Colorectal Cancer Cells

Faqar-Uz-Zaman

Schmidt

Thomas

et al. 2020

Lipids

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Sphingosine-1-phosphate lyase 1 (S1P lyase or SGPL1) is an essential sphingosine-1-phosphate-degrading enzyme. Its manipulation favors onset and progression of colorectal cancer and others in vivo. Thus, SGPL1 is an important modulator of cancer initiation. However, in established cancer, the impact of retrospective SGPL1 modulation is elusive. Herein, we analyzed how SGPL1 siRNA affects malignancy of the human colorectal cancer cells DLD-1 and found that in parallel to the reduction of SGPL1 expression levels, migration, invasion, and differentiation status changed. Diminished SGPL1 expression was accompanied with reduced cell migration and cell invasion in scratch assays and transwell assays, whereas metabolic activity and proliferation was not altered. Decreased migration was attended by increased cell-celladhesion through upregulation of E-cadherin and formation of cadherin-actin complexes. Spreading cell islets showed lower vimentin abundance in border cells. Furthermore, SGPL1 siRNA treatment induced expression of epithelial cell differentiation markers, such as intestinal alkaline phosphatase and cytokeratin 20. Hence, interference with SGPL1 expression augmented a partial redifferentiation of colorectal cancer cells toward normal colon epithelial cells. Our investigation showed that SGPL1 siRNA influenced tumorigenic activity of established colorectal cancer cells. We therefore suggest SGPL1 as a target for lowering malignant potential of already existing cancer. Keywords S1P lyase Á migration Á invasion Á epithelialmesenchymal transition Á differentiation Lipids (2020).

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“…Here, STAT1 , the first member of signal transducer and activator of transcription (STAT) family, has been involved in cancer suppression, including CRC (Zamanian-Azodi and Rezaei-Tavirani, 2019). Schwiebs et al (2019) found that STAT1 has involved in the process of tumor immune microenvironment during the crosstalk of “inflammation-to-tumor.” NF-kappa-B1 ( NF-κB1 ) signaling is a prominent and widely studied inflammatory signaling cascade in the field of immunology (Eden et al, 2017). Increased transcription of NF-κB is associated with inflammation and angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Genes Involved in Ulcerative Colitis Activity and Tumorigenesis Through Systematic Mining of Gene Co-expression Networks

et al. 2019

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Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disorder of the colon, characterized by continuous mucosal inflammation. Recently, some studies have considered it as part of an inflammatory bowel disease-based global network. Herein, with the aim of identifying the underlying potential genetic mechanisms involved in the development of UC, multiple algorithms for weighted correlation network analysis (WGCNA), principal component analysis (PCA), and linear models for microarray data algorithm (LIMMA) were used to identify the hub genes. The map of platelet activation, ligand-receptor interaction, calcium signaling pathway, and cAMP signaling pathway showed significant links with UC development, and the hub genes CCR7, CXCL10, CXCL9, IDO1, MMP9, and VCAM1, which are associated with immune dysregulation and tumorigenesis in biological function, were found by multiple powerful bioinformatics methods. Analysis of The Cancer Genome Atlas (TCGA) also showed that the low expression of CCR7, CXCL10, CXCL9, and MMP9 may be correlated with a poor prognosis of overall survival (OS) in colorectal cancer (CRC) patients (all p < 0.05), while no significance detected in both of IDO1 and VCAM1. In addition, low expression of CCR7, CXCL10, CXCL9, MMP9, and IDO1 may be associated with a poor prognosis in recurrence free survival (RFS) time (all p < 0.05), but no significant difference was identified in VCAM1. Moreover, the NFKB1, FLI1, and STAT1 with the highest enrichment score were detected as the master regulators of hub genes. In summary, these results indicated the central role of the hub genes of CCR7, CXCL10, CXCL9, IDO1, VCAM1, and MMP9, in response to UC progression, as well as the development of UC to CRC, thus shedding light on the molecular mechanisms involved and assisting with drug target validation.

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Cancer-induced inflammation and inflammation-induced cancer in colon: a role for S1P lyase

Cited by 31 publications

References 58 publications

Heterogenous Nuclear Ribonucleoprotein H1 Promotes Colorectal Cancer Progression through the Stabilization of mRNA of Sphingosine-1-Phosphate Lyase 1

Heterogenous Nuclear Ribonucleoprotein H1 Promotes Colorectal Cancer Progression through the Stabilization of mRNA of Sphingosine-1-Phosphate Lyase 1

S1P Lyase siRNA Dampens Malignancy of DLD‐1 Colorectal Cancer Cells

Analysis of Genes Involved in Ulcerative Colitis Activity and Tumorigenesis Through Systematic Mining of Gene Co-expression Networks

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