Biological function of SPNS2: From zebrafish to human

Zhu, Xiao Feng; Zeng, Yanhua; Zheng, Zhoushun; Yi, Guanghui

doi:10.1016/j.molimm.2018.08.025

Cited by 22 publications

(18 citation statements)

References 67 publications

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“…As a transporter of S1P, SPNS2 plays an important role in the release and function of S1P . SPNS2‐induced S1P secretion is necessary for naïve T cell circulation and survival, which is beneficial for adaptive immune responses, but it may contribute to autoreactive and malignant cell survival .…”

Section: Discussionmentioning

confidence: 99%

SPNS2 promotes the malignancy of colorectal cancer cells via regulating Akt and ERK pathway

Jiang

Wang

et al. 2019

Clin Exp Pharma Physio

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Colorectal cancer (CRC) is a prevalent malignant tumour that causes considerable cancer‐related deaths globally. The sphingolipid transporter 2 (SPNS2), a sphingosine‐1‐phosphate (S1P) transporter, modulates multiple biological events including malignancy of cancer cells. In this study, the effects of SPNS2 on CRC progression were studied. We found that SPNS2 expression was significantly upregulated in CRC tissues compared to that in adjacent non‐tumour tissues. To assess the role of SPNS2 in CRC cells, we performed loss‐ and gain‐of‐function experiments in SW480 and HCT116 cells, respectively. The results demonstrated that SPNS2 promoted proliferation, migration and invasion, and inhibited apoptosis in CRC cells. Additionally, SPNS2 enhanced the release of intracellular S1P, and increased S1P receptor 1 (S1PR1) and S1PR3 expression. Moreover, SPNS2 activated the Akt and ERK pathways, and the biological behaviours of SPNS2 were attenuated by Akt or ERK inhibitor in HCT116 cells. In conclusion, our results demonstrated that SPNS2 promoted proliferation, migration and invasion, and inhibited apoptosis by regulating S1P/S1PR1/3 axis and activating Akt and ERK pathway in CRC cells.

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Section: Discussionmentioning

confidence: 99%

SPNS2 promotes the malignancy of colorectal cancer cells via regulating Akt and ERK pathway

Jiang

Wang

et al. 2019

Clin Exp Pharma Physio

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“…The CFA5 locus is associated with HS and lymphoma risk in BMDs, and the top SNVs of this locus are located in an intron of the SPNS3 gene. However, very little is known about this gene although its paralogous gene (SPNS2) is important in immunological development, and plays a critical role in inflammatory and autoimmune diseases, influences lymphocyte trafficking and lymphatic vessel network organization, and drives defective macrophage phagocytic functions [37,56]. Moreover, this region is associated in human GWAS with chemokine CLL2 [57].…”

Section: Genetic Predisposition Of Hs In Three Most At Risk Dog Breeds (Cfa2 Cfa5 Cfa11 Cfa14 and Cfa20)mentioning

confidence: 99%

Identification of common predisposing loci to hematopoietic cancers in four dog breeds

et al. 2021

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Histiocytic sarcoma (HS) is a rare but aggressive cancer in both humans and dogs. The spontaneous canine model, which has clinical, epidemiological, and histological similarities with human HS and specific breed predispositions, provides a unique opportunity to unravel the genetic basis of this cancer. In this study, we aimed to identify germline risk factors associated with the development of HS in canine-predisposed breeds. We used a methodology that combined several genome-wide association studies in a multi-breed and multi-cancer approach as well as targeted next-generation sequencing, and imputation We combined several dog breeds (Bernese mountain dogs, Rottweilers, flat-coated retrievers, and golden retrievers), and three hematopoietic cancers (HS, lymphoma, and mast cell tumor). Results showed that we not only refined the previously identified HS risk CDKN2A locus, but also identified new loci on canine chromosomes 2, 5, 14, and 20. Capture and targeted sequencing of specific loci suggested the existence of regulatory variants in non-coding regions and methylation mechanisms linked to risk haplotypes, which lead to strong cancer predisposition in specific dog breeds. We also showed that these canine cancer predisposing loci appeared to be due to the additive effect of several risk haplotypes involved in other hematopoietic cancers such as lymphoma or mast cell tumors as well. This illustrates the pleiotropic nature of these canine cancer loci as observed in human oncology, thereby reinforcing the interest of predisposed dog breeds to study cancer initiation and progression.

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“…The top CFA5 locus SNVs are located in an intron of the SPNS3 gene (sphingolipid transporter 3). Very few is known about this gene although its paralogous gene (SPNS2) is known to be important in immunological development, playing a critical role in inflammatory and autoimmune diseases, influencing lymphocyte trafficking and lymphatic vessel network organization and driving defective macrophage phagocytic function (https://www.ncbi.nlm.nih.gov/gene/124976, 49 ). Moreover this region is associated in human GWAS with the chemokine CLL2.…”

Section: The Genetic Predisposition Of Histiocytic Sarcoma In 3 Dog Bmentioning

confidence: 99%

The tree that hides the forest: identification of common predisposing loci in several hematopoietic cancers and several dog breeds

Hédan¹,

Cadieu²,

Rimbault³

et al. 2020

Preprint

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Histiocytic sarcoma (HS) is a rare but aggressive cancer in humans and dogs. The spontaneous canine model, with the clinical, epidemiological and histological similarities with human HS and specific breed predispositions, is a unique model/opportunity to unravel the genetic bases of this cancer. In this study, we aimed to identify germline risk factors associated with the development of HS in canine predisposed breeds. We used a methodology that combined several genome-wide association studies in a multi-breed and multi-cancer approach, as well as targeted next generation sequencing, and imputation combining several breeds (Bernese mountain dog, Rottweiler, flat coated retriever and golden retriever) and three haematopoietic cancers (HS, lymphoma and mast cell tumor). Results showed that we not only refined the previously identified HS risk CDKN2A locus but we identified new loci on canine chromosomes 2, 5, 12, 14, 20, 26 and X. Capture and targeted sequencing of specific loci pointed towards the existence of regulatory variants in non coding regions and/or methylation mechanisms linked to risk haplotypes, leading to strong cancer predispositions in specific dog breeds. Our results showed that these canine cancer predisposing loci appear to be due to the additive effect of several risk haplotype involved also in other haematopoietic cancers such lymphoma or mast cell tumor, illustrating the pleiotropic nature of these canine cancer loci as observed in human oncology, thus reinforcing the interest of predisposed dog breeds to study cancer initiation and progression.

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Biological function of SPNS2: From zebrafish to human

Cited by 22 publications

References 67 publications

SPNS2 promotes the malignancy of colorectal cancer cells via regulating Akt and ERK pathway

SPNS2 promotes the malignancy of colorectal cancer cells via regulating Akt and ERK pathway

Identification of common predisposing loci to hematopoietic cancers in four dog breeds

The tree that hides the forest: identification of common predisposing loci in several hematopoietic cancers and several dog breeds

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