Regulation of cancer cell migration and invasion by sphingosine-1-phosphate

Brocklyn, James R. Van

doi:10.4331/wjbc.v1.i10.307

Cited by 23 publications

(23 citation statements)

References 66 publications

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“…Research has shown that the alterations of various oncogenes, tumor suppressor genes, metastasis suppressor genes, and growth factors and their receptors are associated with tumor metastasis [21][22][23]. The fact that Stat3 is activated by numerous cytokines, growth factors, and oncogenic proteins suggests that Stat3 signaling may be one of the common pathways involved in regulating cancer metastasis [4,8,9].…”

Section: Discussionmentioning

confidence: 99%

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Stat3 promotes invasion of esophageal squamous cell carcinoma through up-regulation of MMP2

Xuan

Lou

et al. 2014

Mol Biol Rep

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Stat3 alters the expression of its downstream genes and is associated with tumor invasion and metastasis in several human cancers. Its role in esophageal squamous cell carcinoma (ESCC) has not been well characterized. We examined the tumor sections of 100 cases of ESCC by immunohistochemistry and observed significant overexpression of Stat3 in the cytoplasm of 89% of ESCC cells and of phosphorylated Stat3 (p-Stat3) in the nuclei of 71% of ESCC when compare with normal esophageal mucosa (72%, p = 0.02; and 31%, p = 0.001). Overexpression of Stat3 and p-Stat3 positively correlated with that of matrix metalloproteinase-2 (MMP2), a known regulator for cell migration, in 65% of ESCC while only 26% shown in benign esophageal mucosa. To further investigate the association of Stat3 with tumor metastasis in vitro, invasion of EC-1 cells (a human ESCC cell line) were investigated with Boyden chambers. The results showed that transfection of Stat3 not only promoted invasion of EC-1 cells but also significantly induced MMP2 expression in a dose-dependent manner. In contrast, suppressing expression of endogenous Stat3 mRNA and protein by Stat3 siRNA significantly reduced EC-1 cell invasion and MMP2 expression. A high-affinity Stat3-binding element was localized to the positions of 648-641 bp (TTCTCGAA) in the MMP2 promoter with electrophoretic mobility shift assay. Our results suggest that Stat3, p-Stat3, and MMP2 were overexpressed in ESCC and associated with invasion of ESCC; and Stat3 up-regulated expression of MMP2 in ESCC through directly binding to the MMP2 promoter.

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Section: Discussionmentioning

confidence: 99%

“…Metastasis is a complex process and the major cause of death in most cancer patients [21][22][23]. Understanding its molecular mechanisms will explore the future directions for more effective biological treatment for cancer patients.…”

Section: Discussionmentioning

confidence: 99%

Stat3 promotes invasion of esophageal squamous cell carcinoma through up-regulation of MMP2

Xuan

Lou

et al. 2014

Mol Biol Rep

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“…The role of S1P in both of these processes was recently reviewed [103], and thus, we will only briefly summarize the major findings. The S1P-mediated effect on migration is determined in part by the relative predominance of expressed S1PRs.…”

Section: S1p Migration Invasion and Metastasismentioning

confidence: 99%

“…The diverse physiological processes specifically regulated by the extracellular S1P in a given cell type therefore depend on the repertoire of expressed S1PRs, which couple to various G-proteins and activate numerous signaling pathways. More complete reviews of the downstream signaling of each receptor were published [102][103][104][105]. S1PR1, formerly known as EDG1, was the first identified S1P receptor [89].…”

Section: Extracellular S1pmentioning

confidence: 99%

Extracellular and intracellular sphingosine-1-phosphate in cancer

Yester

Tizazu

Harikumar

et al. 2011

Cancer Metastasis Rev

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Sphingosine-1-phosphate (S1P) was first described as a signaling molecule over 20 years ago. Since then, great strides have been made to reveal its vital roles in vastly different cellular and disease processes. Initially, S1P was considered nothing more than the terminal point of sphingolipid metabolism; however, over the past two decades, a large number of reports have helped unveil its full potential as an important regulatory, bioactive sphingolipid metabolite. S1P has a plethora of physiological functions, due in part to its many sites of actions and its different pools, which are both intra- and extracellular. S1P plays pivotal roles in many physiological processes, including the regulation of cell growth, migration, autophagy, angiogenesis, and survival, and thus, not surprisingly, S1P has been linked to cancer. In this review, we will summarize the vast body of knowledge, highlighting the connection between S1P and cancer. We will also suggest new avenues for future research.

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“…[102] In addition, these effects of S1P are mediated via receptor-dependent pathways that activate different receptors and attribute to diverse effects in various cell lines as we explain later. Hence, S1P1, S1P3, and S1P5 activate cell migration [ Figure 1] through Rac and PLC signaling, despite the fact that S1P2 plays an antimigration effect by Rho signaling.…”

Section: S1p In Tumor Invasion Migration and Metastasismentioning

confidence: 98%

Sphingosin 1-phosphate contributes in tumor progression

et al. 2013

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Sphingosine-1 phosphate (S1P) is a bioactive lipid that mediates diverse cellular responses. Signaling of S1P is carried out by a family of G-protein coupled receptors (GPCRs), which show differential expression patterns depending on tissue and cell types. Activation of S1P receptors induces signaling pathway, which can subsequently lead to physiological process. Intercellular S1P concentration is regulated and determined by several enzymes including S1P lyase, S1P kinase and S1P phosphatase. Numerous studies showed the role of S1P in malignant behavior of cancer cells including breast, lung, colon, and leukemia cell lines. In the past decade, extensive research activities have focused on elucidating S1P signaling pathway, its receptors, enzymes involved in S1P metabolism, and its performance in cancer biology. In this review, we will explain the function of S1P in tumor progression that demonstrated in past research articles and we will express its importance as a target for designing futuristic anticancer drug.

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Regulation of cancer cell migration and invasion by sphingosine-1-phosphate

Cited by 23 publications

References 66 publications

Stat3 promotes invasion of esophageal squamous cell carcinoma through up-regulation of MMP2

Stat3 promotes invasion of esophageal squamous cell carcinoma through up-regulation of MMP2

Extracellular and intracellular sphingosine-1-phosphate in cancer

Sphingosin 1-phosphate contributes in tumor progression

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