Critical role of Spns2, a sphingosine-1-phosphate transporter, in lung cancer cell survival and migration

Eric Bradley, Somsankar Dasgupta, Xue Jiang, Xiaying Zhao, Gu Zhu, Qian He, Michael Dinkins, Erhard Bieberich, Guanghu Wang

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

The sphingosine-1-phosphate (S1P) transporter Spns2 regulates myocardial precursor migration in zebrafish and lymphocyte trafficking in mice. However, its function in cancer has not been investigated. We show here that ectopic Spns2 expression induced apoptosis and its knockdown enhanced cell migration in non-small cell lung cancer (NSCLC) cells. Metabolically, Spns2 expression increased the extracellular S1P level while its knockdown the intracellular. Pharmacological inhibition of S1P synthesis abolished the augmented cell migration mediated by Spns2 knockdown, indicating that intracellular S1P plays a key role in this process. Cell signaling studies indicated that Spns2 expression impaired GSK-3b and Stat3 mediated pro-survival pathways. Conversely, these pathways were activated by Spns2 knockdown, which explains the increased cell migration since they are also crucial for migration. Alterations of Spns2 were found to affect several enzymes involved in S1P metabolism, including sphingosine kinases, S1P phosphatases, and S1P lyase 1. Genetically, Spns2 mRNA level was found to be reduced in advanced lung cancer (LC) patients as quantified by using a small scale qPCR array. These data show for the first time that Spns2 plays key roles in regulating the cellular functions in NSCLC cells, and that its down-regulation is a potential risk factor for LC.

Original languageEnglish (US)
Article numbere110119
JournalPloS one
Volume9
Issue number10
DOIs
StatePublished - Oct 20 2014

Fingerprint

Phosphate Transport Proteins
sphingosine
lung neoplasms
cell movement
Cell Movement
cell viability
transporters
Lung Neoplasms
Cell Survival
Cells
phosphates
Non-Small Cell Lung Carcinoma
Cell signaling
Lymphocytes
Zebrafish
Metabolism
Down-Regulation
neoplasm cells
sphingosine 1-phosphate
lyases

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Bradley, E., Dasgupta, S., Jiang, X., Zhao, X., Zhu, G., He, Q., ... Wang, G. (2014). Critical role of Spns2, a sphingosine-1-phosphate transporter, in lung cancer cell survival and migration. PloS one, 9(10), [e110119]. https://doi.org/10.1371/journal.pone.0110119

Critical role of Spns2, a sphingosine-1-phosphate transporter, in lung cancer cell survival and migration. / Bradley, Eric; Dasgupta, Somsankar; Jiang, Xue; Zhao, Xiaying; Zhu, Gu; He, Qian; Dinkins, Michael; Bieberich, Erhard; Wang, Guanghu.

In: PloS one, Vol. 9, No. 10, e110119, 20.10.2014.

Research output: Contribution to journalArticle

Bradley, E, Dasgupta, S, Jiang, X, Zhao, X, Zhu, G, He, Q, Dinkins, M, Bieberich, E & Wang, G 2014, 'Critical role of Spns2, a sphingosine-1-phosphate transporter, in lung cancer cell survival and migration', PloS one, vol. 9, no. 10, e110119. https://doi.org/10.1371/journal.pone.0110119
Bradley, Eric ; Dasgupta, Somsankar ; Jiang, Xue ; Zhao, Xiaying ; Zhu, Gu ; He, Qian ; Dinkins, Michael ; Bieberich, Erhard ; Wang, Guanghu. / Critical role of Spns2, a sphingosine-1-phosphate transporter, in lung cancer cell survival and migration. In: PloS one. 2014 ; Vol. 9, No. 10.
@article{f1167dd7642148cbb44a0c8895dfd2e0,
title = "Critical role of Spns2, a sphingosine-1-phosphate transporter, in lung cancer cell survival and migration",
abstract = "The sphingosine-1-phosphate (S1P) transporter Spns2 regulates myocardial precursor migration in zebrafish and lymphocyte trafficking in mice. However, its function in cancer has not been investigated. We show here that ectopic Spns2 expression induced apoptosis and its knockdown enhanced cell migration in non-small cell lung cancer (NSCLC) cells. Metabolically, Spns2 expression increased the extracellular S1P level while its knockdown the intracellular. Pharmacological inhibition of S1P synthesis abolished the augmented cell migration mediated by Spns2 knockdown, indicating that intracellular S1P plays a key role in this process. Cell signaling studies indicated that Spns2 expression impaired GSK-3b and Stat3 mediated pro-survival pathways. Conversely, these pathways were activated by Spns2 knockdown, which explains the increased cell migration since they are also crucial for migration. Alterations of Spns2 were found to affect several enzymes involved in S1P metabolism, including sphingosine kinases, S1P phosphatases, and S1P lyase 1. Genetically, Spns2 mRNA level was found to be reduced in advanced lung cancer (LC) patients as quantified by using a small scale qPCR array. These data show for the first time that Spns2 plays key roles in regulating the cellular functions in NSCLC cells, and that its down-regulation is a potential risk factor for LC.",
author = "Eric Bradley and Somsankar Dasgupta and Xue Jiang and Xiaying Zhao and Gu Zhu and Qian He and Michael Dinkins and Erhard Bieberich and Guanghu Wang",
year = "2014",
month = "10",
day = "20",
doi = "10.1371/journal.pone.0110119",
language = "English (US)",
volume = "9",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "10",

}

TY - JOUR

T1 - Critical role of Spns2, a sphingosine-1-phosphate transporter, in lung cancer cell survival and migration

AU - Bradley, Eric

AU - Dasgupta, Somsankar

AU - Jiang, Xue

AU - Zhao, Xiaying

AU - Zhu, Gu

AU - He, Qian

AU - Dinkins, Michael

AU - Bieberich, Erhard

AU - Wang, Guanghu

PY - 2014/10/20

Y1 - 2014/10/20

N2 - The sphingosine-1-phosphate (S1P) transporter Spns2 regulates myocardial precursor migration in zebrafish and lymphocyte trafficking in mice. However, its function in cancer has not been investigated. We show here that ectopic Spns2 expression induced apoptosis and its knockdown enhanced cell migration in non-small cell lung cancer (NSCLC) cells. Metabolically, Spns2 expression increased the extracellular S1P level while its knockdown the intracellular. Pharmacological inhibition of S1P synthesis abolished the augmented cell migration mediated by Spns2 knockdown, indicating that intracellular S1P plays a key role in this process. Cell signaling studies indicated that Spns2 expression impaired GSK-3b and Stat3 mediated pro-survival pathways. Conversely, these pathways were activated by Spns2 knockdown, which explains the increased cell migration since they are also crucial for migration. Alterations of Spns2 were found to affect several enzymes involved in S1P metabolism, including sphingosine kinases, S1P phosphatases, and S1P lyase 1. Genetically, Spns2 mRNA level was found to be reduced in advanced lung cancer (LC) patients as quantified by using a small scale qPCR array. These data show for the first time that Spns2 plays key roles in regulating the cellular functions in NSCLC cells, and that its down-regulation is a potential risk factor for LC.

AB - The sphingosine-1-phosphate (S1P) transporter Spns2 regulates myocardial precursor migration in zebrafish and lymphocyte trafficking in mice. However, its function in cancer has not been investigated. We show here that ectopic Spns2 expression induced apoptosis and its knockdown enhanced cell migration in non-small cell lung cancer (NSCLC) cells. Metabolically, Spns2 expression increased the extracellular S1P level while its knockdown the intracellular. Pharmacological inhibition of S1P synthesis abolished the augmented cell migration mediated by Spns2 knockdown, indicating that intracellular S1P plays a key role in this process. Cell signaling studies indicated that Spns2 expression impaired GSK-3b and Stat3 mediated pro-survival pathways. Conversely, these pathways were activated by Spns2 knockdown, which explains the increased cell migration since they are also crucial for migration. Alterations of Spns2 were found to affect several enzymes involved in S1P metabolism, including sphingosine kinases, S1P phosphatases, and S1P lyase 1. Genetically, Spns2 mRNA level was found to be reduced in advanced lung cancer (LC) patients as quantified by using a small scale qPCR array. These data show for the first time that Spns2 plays key roles in regulating the cellular functions in NSCLC cells, and that its down-regulation is a potential risk factor for LC.

UR - http://www.scopus.com/inward/record.url?scp=84908191417&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84908191417&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0110119

DO - 10.1371/journal.pone.0110119

M3 - Article

C2 - 25330231

AN - SCOPUS:84908191417

VL - 9

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 10

M1 - e110119

ER -