Activation of sphingosine kinase by lipopolysaccharide promotes prostate cancer cell invasion and metastasis via SphK1/S1PR4/matriptase

Cheng Fan Lee, Andrew Dang, Elizabeth Hernandez, Rey Chen Pong, Ping-chi B Chen, Rajni Sonavane, Ganesh Raj, Payal Kapur, Hsin Ying Lin, Shang Ru Wu, Chun Jung Ko, U. Ging Lo, Hsin yu Lee, Jer-Tsong Hsieh, Ming Shyue Lee

Research output: Contribution to journalArticle

Abstract

Gram-negative bacteria have been found to be a major population in prostatitis and prostate cancer (PCa) tissues. Lipopolysaccharide (LPS), a major compound of Gram-negative bacteria, with stimulatory activities in some cancer types, but has not been fully studied in PCa. In this study, we examined the effect of LPS on the invasion of PCa cells. Interestingly, LPS can enhance the invasiveness of PCa, but had no significant effect on PCa cell viability. Using protease inhibitor screening and biochemical analyses, matriptase, a member of the membrane-anchored serine protease family, is found to play a key role in LPS-induced PCa cell invasion. Mechanistically, Toll-like receptor 4 (TLR4, LPS receptor)-sphingosine kinase 1 (SphK1) signaling underlies LPS-induced matriptase activation and PCa cell invasion. Specifically, LPS induced the S225 phosphorylation of SphK1 and the translocation of SphK1 to plasma membrane, leading to the production of sphingosine 1-phosphate (S1P), ERK1/2 and matriptase activation via S1P receptor 4 (S1PR4). This phenomenon is further validated using the patient-derived explant (PDE) model. Indeed, there is a significant correlation among the elevated SphK1 levels, the Gleason grades of PCa specimens, and the poor survival of PCa patients. Taken together, this study demonstrates a potential impact of LPS on PCa progression. Our results provide not only a new finding of the role of bacterial infection in PCa progression but also potential therapeutic target(s) associated with PCa metastasis.

Original languageEnglish (US)
JournalOncogene
DOIs
StatePublished - Jan 1 2019

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Lysosphingolipid Receptors
Lipopolysaccharides
Prostatic Neoplasms
Neoplasm Metastasis
Toll-Like Receptor 4
Gram-Negative Bacteria
sphingosine kinase
matriptase
CD14 Antigens
Prostatitis
Serine Proteases
Protease Inhibitors
Bacterial Infections

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Activation of sphingosine kinase by lipopolysaccharide promotes prostate cancer cell invasion and metastasis via SphK1/S1PR4/matriptase. / Lee, Cheng Fan; Dang, Andrew; Hernandez, Elizabeth; Pong, Rey Chen; Chen, Ping-chi B; Sonavane, Rajni; Raj, Ganesh; Kapur, Payal; Lin, Hsin Ying; Wu, Shang Ru; Ko, Chun Jung; Lo, U. Ging; Lee, Hsin yu; Hsieh, Jer-Tsong; Lee, Ming Shyue.

In: Oncogene, 01.01.2019.

Research output: Contribution to journalArticle

Lee, Cheng Fan ; Dang, Andrew ; Hernandez, Elizabeth ; Pong, Rey Chen ; Chen, Ping-chi B ; Sonavane, Rajni ; Raj, Ganesh ; Kapur, Payal ; Lin, Hsin Ying ; Wu, Shang Ru ; Ko, Chun Jung ; Lo, U. Ging ; Lee, Hsin yu ; Hsieh, Jer-Tsong ; Lee, Ming Shyue. / Activation of sphingosine kinase by lipopolysaccharide promotes prostate cancer cell invasion and metastasis via SphK1/S1PR4/matriptase. In: Oncogene. 2019.
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abstract = "Gram-negative bacteria have been found to be a major population in prostatitis and prostate cancer (PCa) tissues. Lipopolysaccharide (LPS), a major compound of Gram-negative bacteria, with stimulatory activities in some cancer types, but has not been fully studied in PCa. In this study, we examined the effect of LPS on the invasion of PCa cells. Interestingly, LPS can enhance the invasiveness of PCa, but had no significant effect on PCa cell viability. Using protease inhibitor screening and biochemical analyses, matriptase, a member of the membrane-anchored serine protease family, is found to play a key role in LPS-induced PCa cell invasion. Mechanistically, Toll-like receptor 4 (TLR4, LPS receptor)-sphingosine kinase 1 (SphK1) signaling underlies LPS-induced matriptase activation and PCa cell invasion. Specifically, LPS induced the S225 phosphorylation of SphK1 and the translocation of SphK1 to plasma membrane, leading to the production of sphingosine 1-phosphate (S1P), ERK1/2 and matriptase activation via S1P receptor 4 (S1PR4). This phenomenon is further validated using the patient-derived explant (PDE) model. Indeed, there is a significant correlation among the elevated SphK1 levels, the Gleason grades of PCa specimens, and the poor survival of PCa patients. Taken together, this study demonstrates a potential impact of LPS on PCa progression. Our results provide not only a new finding of the role of bacterial infection in PCa progression but also potential therapeutic target(s) associated with PCa metastasis.",
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AU - Lee, Cheng Fan

AU - Dang, Andrew

AU - Hernandez, Elizabeth

AU - Pong, Rey Chen

AU - Chen, Ping-chi B

AU - Sonavane, Rajni

AU - Raj, Ganesh

AU - Kapur, Payal

AU - Lin, Hsin Ying

AU - Wu, Shang Ru

AU - Ko, Chun Jung

AU - Lo, U. Ging

AU - Lee, Hsin yu

AU - Hsieh, Jer-Tsong

AU - Lee, Ming Shyue

PY - 2019/1/1

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AB - Gram-negative bacteria have been found to be a major population in prostatitis and prostate cancer (PCa) tissues. Lipopolysaccharide (LPS), a major compound of Gram-negative bacteria, with stimulatory activities in some cancer types, but has not been fully studied in PCa. In this study, we examined the effect of LPS on the invasion of PCa cells. Interestingly, LPS can enhance the invasiveness of PCa, but had no significant effect on PCa cell viability. Using protease inhibitor screening and biochemical analyses, matriptase, a member of the membrane-anchored serine protease family, is found to play a key role in LPS-induced PCa cell invasion. Mechanistically, Toll-like receptor 4 (TLR4, LPS receptor)-sphingosine kinase 1 (SphK1) signaling underlies LPS-induced matriptase activation and PCa cell invasion. Specifically, LPS induced the S225 phosphorylation of SphK1 and the translocation of SphK1 to plasma membrane, leading to the production of sphingosine 1-phosphate (S1P), ERK1/2 and matriptase activation via S1P receptor 4 (S1PR4). This phenomenon is further validated using the patient-derived explant (PDE) model. Indeed, there is a significant correlation among the elevated SphK1 levels, the Gleason grades of PCa specimens, and the poor survival of PCa patients. Taken together, this study demonstrates a potential impact of LPS on PCa progression. Our results provide not only a new finding of the role of bacterial infection in PCa progression but also potential therapeutic target(s) associated with PCa metastasis.

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