Spinster homolog 2 in cancers, its functions and mechanisms

Fang, Lian; Hou, Jie; Cao, Yihui; Shan, Jiajie; Zhao, Jie

doi:10.1016/j.cellsig.2020.109821

Cited by 13 publications

(10 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although there is an increasing body of evidence supporting the involvement of Spns2 in cancer development and metastasis, its exact role in these processes seems to depend on cancer type, stage, and microenvironment 35 . Expression of Spns2 in colorectal cancer was found to be higher compared to the adjacent healthy tissue.…”

Section: Discussionmentioning

confidence: 92%

Grade‐dependent changes in sphingolipid metabolism in clear cell renal cell carcinoma

Młynarczyk

Mikłosz

Suchański

et al. 2022

J of Cellular Biochemistry

View full text Add to dashboard Cite

There is a host of evidence for the role of bioactive sphingolipids in cancer biology, and dysregulated sphingolipid metabolism was observed in many malignant tumors. The aim of the present study was to provide more detailed data on sphingolipid metabolism in different stages of clear cell renal cell carcinoma (ccRCC). Samples of the tumor and noncancerous fragments of the same kidney were collected from patients who underwent a radical nephrectomy. The subjects were stratified according to the degree of malignancy of the tumor (n = 14 for G2, 12 for G3, and 9 for G4). The content of bioactive sphingolipids/glycosphingolipids was measured with an HPLC and HPTLC method, and the mRNA and protein expression of sphingolipid transporters and metabolizing enzymes was evaluated using real‐time polymerase chain reaction (PCR) and Western blot, respectively. Compared to healthy kidney tissue, ccRCC was characterized by accumulation of sphingosine, sphingosine‐1‐phosphate (S1P), ceramide, dihydrosphingosine, and dihydroceramide. However, in the case of the latter two, the accumulation was limited to higher malignancy grades. In addition, compared to the healthy tissue, the content of gangliosides in the tumor was increased at the expense of globosides. We also found profound grade‐dependent changes in the mRNA level of S1P‐metabolizing enzymes, and spinster homolog 2. In general, their expression was much higher in G2 tumors compared to higher malignancy grades. We conclude that ccRCC is characterized by profound and multilevel alterations in sphingolipid metabolism, which to a large extent are grade‐dependent. We hypothesize that dysregulation of sphingolipid metabolism contributes to the progression of ccRCC.

show abstract

Section: Discussionmentioning

confidence: 92%

Grade‐dependent changes in sphingolipid metabolism in clear cell renal cell carcinoma

Młynarczyk

Mikłosz

Suchański

et al. 2022

J of Cellular Biochemistry

View full text Add to dashboard Cite

show abstract

“…S1P, a bioactive sphingolipid metabolite that involved in many physiology and pathology process including cancer genesis and progression, is the transport target of SPNS2. It has been reported that SPNS2 generally showed a promoting effect in the genesis, apoptosis and migration of cancer, through S1P/S1PRs pathways activating downstream signaling such as AKT, STAT3, ERK, Ras and Rac ( 41 ). On the contrary, we found that SPNS2 was significantly downregulated in most types of tumors including LUAD and LUSC, which indicated the tumor suppressor function of SPNS2.…”

Section: Discussionmentioning

confidence: 99%

SPNS2 Downregulation Induces EMT and Promotes Colorectal Cancer Metastasis via Activating AKT Signaling Pathway

Yan

et al. 2021

Front. Oncol.

View full text Add to dashboard Cite

Spinster homologue 2 (SPNS2), a transporter of S1P (sphingosine-1-phosphate), has been reported to mediate immune response, vascular development, and pathologic processes of diseases such as cancer via S1P signaling pathways. However, its biological functions and expression profile in colorectal cancer (CRC) is elusive. In this study, we disclosed that SPNS2 expression, which was regulated by copy number variation and DNA methylation of its promoter, was dramatically upregulated in colon adenoma and CRC compared to normal tissues. However, its expression was lower in CRC than in colon adenoma, and low expression of SPN2 correlated with advanced T/M/N stage and poor prognosis in CRC. Ectopic expression of SPNS2 inhibited cell proliferation, migration, epithelial–mesenchymal transition (EMT), invasion, and metastasis in CRC cell lines, while silencing SPNS2 had the opposite effects. Meanwhile, measuring the intracellular and extracellular level of S1P after overexpression of SPNS2 pinpointed a S1P-independent model of SPNS2. Mechanically, SPNS2 led to PTEN upregulation and inactivation of Akt. Moreover, AKT inhibitor (MK2206) abrogated SPNS2 knockdown-induced promoting effects on the migration and invasion, while AKT activator (SC79) reversed the repression of migration and invasion by SPNS2 overexpression in CRC cells, confirming the pivotal role of AKT for SPNS2’s function. Collectively, our study demonstrated the suppressor role of SPNS2 during CRC metastasis, providing new insights into the pathology and molecular mechanisms of CRC progression.

show abstract

“…Under these conditions, amino acids are also more rapidly converted to proteins [ 7 , 8 ]. These combined actions support the rapid cellular duplication that is characteristic of cancer cells [ 9 , 10 ]. The upregulation of the pentose phosphate pathway also augments the production of pentoses and NADPH [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Anti-Warburg Effect of Melatonin: A Proposed Mechanism to Explain its Inhibition of Multiple Diseases

Reíter

Sharma

Rosales-Corral

2021

IJMS

View full text Add to dashboard Cite

Glucose is an essential nutrient for every cell but its metabolic fate depends on cellular phenotype. Normally, the product of cytosolic glycolysis, pyruvate, is transported into mitochondria and irreversibly converted to acetyl coenzyme A by pyruvate dehydrogenase complex (PDC). In some pathological cells, however, pyruvate transport into the mitochondria is blocked due to the inhibition of PDC by pyruvate dehydrogenase kinase. This altered metabolism is referred to as aerobic glycolysis (Warburg effect) and is common in solid tumors and in other pathological cells. Switching from mitochondrial oxidative phosphorylation to aerobic glycolysis provides diseased cells with advantages because of the rapid production of ATP and the activation of pentose phosphate pathway (PPP) which provides nucleotides required for elevated cellular metabolism. Molecules, called glycolytics, inhibit aerobic glycolysis and convert cells to a healthier phenotype. Glycolytics often function by inhibiting hypoxia-inducible factor-1α leading to PDC disinhibition allowing for intramitochondrial conversion of pyruvate into acetyl coenzyme A. Melatonin is a glycolytic which converts diseased cells to the healthier phenotype. Herein we propose that melatonin’s function as a glycolytic explains its actions in inhibiting a variety of diseases. Thus, the common denominator is melatonin’s action in switching the metabolic phenotype of cells.

show abstract

Spinster homolog 2 in cancers, its functions and mechanisms

Cited by 13 publications

References 74 publications

Grade‐dependent changes in sphingolipid metabolism in clear cell renal cell carcinoma

Grade‐dependent changes in sphingolipid metabolism in clear cell renal cell carcinoma

SPNS2 Downregulation Induces EMT and Promotes Colorectal Cancer Metastasis via Activating AKT Signaling Pathway

Anti-Warburg Effect of Melatonin: A Proposed Mechanism to Explain its Inhibition of Multiple Diseases

Contact Info

Product

Resources

About