Skip to main content
Erschienen in: Tumor Biology 5/2016

10.12.2015 | Original Article

SphK1 promotes tumor cell migration and invasion in colorectal cancer

verfasst von: Jianting Long, Ying Xie, Junmei Yin, Wei Lu, Shi Fang

Erschienen in: Tumor Biology | Ausgabe 5/2016

Einloggen, um Zugang zu erhalten

Abstract

Colorectal cancer (CRC) is one of the most common cancers worldwide. Sphingosine kinase 1 (SphK1), which phosphorylates sphingosine to sphingosine-1-phosphate (S1P), is overexpressed in various types of cancers and may act as an oncogene in tumorigenesis. However, little is known about the role of SphK1 in CRC patients. We studied the expression of SphK1 in 85 cases of CRC tissues by immunohistochemistry, qRT-PCR, and western blot. We also evaluated the effect of SphK1 on cell proliferation and invasion by MTT and transwell invasion assay. SphK1 is overexpressed in CRC tissues and cell lines, and upregulation of SphK1 correlated significantly with the following parameters: lymph node metastasis, liver metastasis, and advanced TNM stage. SphK1 knockdown results in inhibition of cancer cell proliferation. Inhibition of CRC cell migration and invasion is also evident through reversal of EMT by increases in E-cadherin expression and decreases in vimentin expression. In conclusion, SphK1 is associated with the proliferation and invasiveness of CRC cells and the SphK1 gene may contribute to a novel therapeutic approach against CRC.
Literatur
1.
2.
Zurück zum Zitat Kobayashi H, Mochizuki H, Sugihara K, Morita T, Kotake K, Teramoto T, et al. Characteristics of recurrence and surveillance tools after curative resection for colorectal cancer: a multicenter study. Surgery. 2007;141:67–75.CrossRefPubMed Kobayashi H, Mochizuki H, Sugihara K, Morita T, Kotake K, Teramoto T, et al. Characteristics of recurrence and surveillance tools after curative resection for colorectal cancer: a multicenter study. Surgery. 2007;141:67–75.CrossRefPubMed
3.
Zurück zum Zitat Lieberman DA, Rex DK, Winawer SJ, Giardiello FM, Johnson DA, Levin TR. Guidelines for colonoscopy surveillance after screening and polypectomy: a consensus update by the US Multi-Society Task Force on colorectal cancer. Gastroenterology. 2012;143:844–57.CrossRefPubMed Lieberman DA, Rex DK, Winawer SJ, Giardiello FM, Johnson DA, Levin TR. Guidelines for colonoscopy surveillance after screening and polypectomy: a consensus update by the US Multi-Society Task Force on colorectal cancer. Gastroenterology. 2012;143:844–57.CrossRefPubMed
4.
Zurück zum Zitat Toiyama Y, Hur K, Tanaka K, Inoue Y, Kusunoki M, Boland CR. Serum miR-200c is a novel prognostic and metastasis-predictive biomarker in patients with colorectal cancer. Ann Surg. 2014;259(4):735–43.CrossRefPubMedPubMedCentral Toiyama Y, Hur K, Tanaka K, Inoue Y, Kusunoki M, Boland CR. Serum miR-200c is a novel prognostic and metastasis-predictive biomarker in patients with colorectal cancer. Ann Surg. 2014;259(4):735–43.CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat Shimada H, Tanaka K, Endou I, Ichikawa Y. Treatment for colorectal liver metastases: a review. Langenbecks Arch Surg. 2009;394:973–83.CrossRefPubMed Shimada H, Tanaka K, Endou I, Ichikawa Y. Treatment for colorectal liver metastases: a review. Langenbecks Arch Surg. 2009;394:973–83.CrossRefPubMed
6.
Zurück zum Zitat Zhang H, Wang Q, Zhao Q, Di W. MiR-124 inhibits the migration and invasion of ovarian cancer cells by targeting SphK1. J Ovarian Res. 2013;6(1):84.CrossRefPubMedPubMedCentral Zhang H, Wang Q, Zhao Q, Di W. MiR-124 inhibits the migration and invasion of ovarian cancer cells by targeting SphK1. J Ovarian Res. 2013;6(1):84.CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Yang YL, Ji C, Cheng L, He L, Lu CC, Wang R, et al. Sphingosine kinase-1 inhibition sensitizes curcumin-induced growth inhibition and apoptosis in ovarian cancer cells. Cancer Sci. 2012;103(8):1538–45.CrossRefPubMed Yang YL, Ji C, Cheng L, He L, Lu CC, Wang R, et al. Sphingosine kinase-1 inhibition sensitizes curcumin-induced growth inhibition and apoptosis in ovarian cancer cells. Cancer Sci. 2012;103(8):1538–45.CrossRefPubMed
8.
Zurück zum Zitat Santulli P, Marcellin L, Noël JC, Borghese B, Fayt I, Vaiman D, et al. Sphingosine pathway deregulation in endometriotic tissues. Fertil Steril. 2012;97(4):904–11.CrossRefPubMed Santulli P, Marcellin L, Noël JC, Borghese B, Fayt I, Vaiman D, et al. Sphingosine pathway deregulation in endometriotic tissues. Fertil Steril. 2012;97(4):904–11.CrossRefPubMed
9.
Zurück zum Zitat Datta A, Loo SY, Huang B, Wong L, Tan SS, Tan TZ, et al. SPHK1 regulates proliferation and survival responses in triple-negative breast cancer. Oncotarget. 2014;5(15):5920–33.CrossRefPubMedPubMedCentral Datta A, Loo SY, Huang B, Wong L, Tan SS, Tan TZ, et al. SPHK1 regulates proliferation and survival responses in triple-negative breast cancer. Oncotarget. 2014;5(15):5920–33.CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Wang Y, Tang Q, Li M, Jiang S, Wang X. MicroRNA-375 inhibits colorectal cancer growth by targeting PIK3CA. Biochem Biophys Res Commun. 2014;444:199–204.CrossRefPubMed Wang Y, Tang Q, Li M, Jiang S, Wang X. MicroRNA-375 inhibits colorectal cancer growth by targeting PIK3CA. Biochem Biophys Res Commun. 2014;444:199–204.CrossRefPubMed
11.
Zurück zum Zitat Van Cutsem E, Nordlinger B, Adam R, K€ohne CH, Pozzo C, Poston G. Towards a pan-European consensus on the treatment of patients with colorectal liver metastases. Eur J Cancer. 2006;42:2212–21.CrossRefPubMed Van Cutsem E, Nordlinger B, Adam R, K€ohne CH, Pozzo C, Poston G. Towards a pan-European consensus on the treatment of patients with colorectal liver metastases. Eur J Cancer. 2006;42:2212–21.CrossRefPubMed
12.
Zurück zum Zitat Meng XD, Zhou ZS, Qiu JH, Shen WH, Wu Q, Xiao J. Increased SPHK1 expression is associated with poor prognosis in bladder cancer. Tumour Biol. 2014;35(3):2075–80.CrossRefPubMed Meng XD, Zhou ZS, Qiu JH, Shen WH, Wu Q, Xiao J. Increased SPHK1 expression is associated with poor prognosis in bladder cancer. Tumour Biol. 2014;35(3):2075–80.CrossRefPubMed
13.
Zurück zum Zitat Lu Z, Zhang W, Gao S, Jiang Q, Xiao Z, Ye L, et al. MiR-506 suppresses liver cancer angiogenesis through targeting sphingosine kinase 1 (SPHK1) mRNA. Biochem Biophys Res Commun. 2015;468(1–2):8–13.CrossRefPubMed Lu Z, Zhang W, Gao S, Jiang Q, Xiao Z, Ye L, et al. MiR-506 suppresses liver cancer angiogenesis through targeting sphingosine kinase 1 (SPHK1) mRNA. Biochem Biophys Res Commun. 2015;468(1–2):8–13.CrossRefPubMed
14.
Zurück zum Zitat Shi J, He YY, Sun JX, Guo WX, Li N, Xue J, et al. The impact of sphingosine kinase 1 on the prognosis of hepatocellular carcinoma patients with portal vein tumor thrombus. Ann Hepatol. 2015;14(2):198–206.PubMed Shi J, He YY, Sun JX, Guo WX, Li N, Xue J, et al. The impact of sphingosine kinase 1 on the prognosis of hepatocellular carcinoma patients with portal vein tumor thrombus. Ann Hepatol. 2015;14(2):198–206.PubMed
15.
Zurück zum Zitat Lufrano M, Jacob A, Zhou M, Wang P. Sphingosine kinase-1 mediates endotoxemia-induced hyperinflammation in aged animals. Mol Med Rep. 2013;8(2):645–9.PubMedPubMedCentral Lufrano M, Jacob A, Zhou M, Wang P. Sphingosine kinase-1 mediates endotoxemia-induced hyperinflammation in aged animals. Mol Med Rep. 2013;8(2):645–9.PubMedPubMedCentral
16.
Zurück zum Zitat Karimian G, Buist-Homan M, Schmidt M, Tietge UJ, de Boer JF, Klappe K, et al. Sphingosine kinase-1 inhibition protects primary rat hepatocytes against bile salt-induced apoptosis. Biochim Biophys Acta. 2013;1832(12):1922–9.CrossRefPubMed Karimian G, Buist-Homan M, Schmidt M, Tietge UJ, de Boer JF, Klappe K, et al. Sphingosine kinase-1 inhibition protects primary rat hepatocytes against bile salt-induced apoptosis. Biochim Biophys Acta. 2013;1832(12):1922–9.CrossRefPubMed
17.
Zurück zum Zitat Fidler IJ, Hart IR. Biological diversity in metastatic neoplasms: origins and implications. Science. 1982;217:998–1003.CrossRefPubMed Fidler IJ, Hart IR. Biological diversity in metastatic neoplasms: origins and implications. Science. 1982;217:998–1003.CrossRefPubMed
18.
Zurück zum Zitat Liotta LA, Steeq PS, Stetler-Stevenson WG. Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell. 1991;64:327–36.CrossRefPubMed Liotta LA, Steeq PS, Stetler-Stevenson WG. Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell. 1991;64:327–36.CrossRefPubMed
19.
Zurück zum Zitat Guillermet-Guibert J, Davenne L, Pchejetski D, Saint-Laurent N, Brizuela L, Guilbeau-Frugier C, et al. Targeting the sphingolipid metabolism to defeat pancreatic cancer cell resistance to the chemotherapeutic gemcitabine drug. Mol Cancer Ther. 2009;8(4):809–20.CrossRefPubMed Guillermet-Guibert J, Davenne L, Pchejetski D, Saint-Laurent N, Brizuela L, Guilbeau-Frugier C, et al. Targeting the sphingolipid metabolism to defeat pancreatic cancer cell resistance to the chemotherapeutic gemcitabine drug. Mol Cancer Ther. 2009;8(4):809–20.CrossRefPubMed
20.
Zurück zum Zitat Vettorazzi S, Bode C, Dejager L, Frappart L, Shelest E, Klaßen C, et al. Glucocorticoids limit acute lung inflammation in concert with inflammatory stimuli by induction of SphK1. Nat Commun. 2015;6:7796.CrossRefPubMedPubMedCentral Vettorazzi S, Bode C, Dejager L, Frappart L, Shelest E, Klaßen C, et al. Glucocorticoids limit acute lung inflammation in concert with inflammatory stimuli by induction of SphK1. Nat Commun. 2015;6:7796.CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Zhu L, Wang Z, Lin Y, Chen Z, Liu H, Chen Y, et al. Sphingosine kinase 1 enhances the invasion and migration of non-small cell lung cancer cells via the AKT pathway. Oncol Rep. 2015;33(3):1257–63.PubMed Zhu L, Wang Z, Lin Y, Chen Z, Liu H, Chen Y, et al. Sphingosine kinase 1 enhances the invasion and migration of non-small cell lung cancer cells via the AKT pathway. Oncol Rep. 2015;33(3):1257–63.PubMed
22.
Zurück zum Zitat Ader I, Gstalder C, Bouquerel P, Golzio M, Andrieu G, Zalvidea S, et al. Neutralizing S1P inhibits intratumoral hypoxia, induces vascular remodelling and sensitizes to chemotherapy in prostate cancer. Oncotarget. 2015;6(15):13803–21.CrossRefPubMedPubMedCentral Ader I, Gstalder C, Bouquerel P, Golzio M, Andrieu G, Zalvidea S, et al. Neutralizing S1P inhibits intratumoral hypoxia, induces vascular remodelling and sensitizes to chemotherapy in prostate cancer. Oncotarget. 2015;6(15):13803–21.CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Cho SY, Cho S, Park E, Kim B, Sohn EJ, Oh B, et al. Coumestrol suppresses hypoxia inducible factor 1α by inhibiting ROS mediated sphingosine kinase 1 in hypoxic PC-3 prostate cancer cells. Bioorg Med Chem Lett. 2014;24(11):2560–4.CrossRefPubMed Cho SY, Cho S, Park E, Kim B, Sohn EJ, Oh B, et al. Coumestrol suppresses hypoxia inducible factor 1α by inhibiting ROS mediated sphingosine kinase 1 in hypoxic PC-3 prostate cancer cells. Bioorg Med Chem Lett. 2014;24(11):2560–4.CrossRefPubMed
Metadaten
Titel
SphK1 promotes tumor cell migration and invasion in colorectal cancer
verfasst von
Jianting Long
Ying Xie
Junmei Yin
Wei Lu
Shi Fang
Publikationsdatum
10.12.2015
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 5/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-4542-4

Weitere Artikel der Ausgabe 5/2016

Tumor Biology 5/2016 Zur Ausgabe

Alphablocker schützt vor Miktionsproblemen nach der Biopsie

16.05.2024 alpha-1-Rezeptorantagonisten Nachrichten

Nach einer Prostatabiopsie treten häufig Probleme beim Wasserlassen auf. Ob sich das durch den periinterventionellen Einsatz von Alphablockern verhindern lässt, haben australische Mediziner im Zuge einer Metaanalyse untersucht.

Antikörper-Wirkstoff-Konjugat hält solide Tumoren in Schach

16.05.2024 Zielgerichtete Therapie Nachrichten

Trastuzumab deruxtecan scheint auch jenseits von Lungenkrebs gut gegen solide Tumoren mit HER2-Mutationen zu wirken. Dafür sprechen die Daten einer offenen Pan-Tumor-Studie.

Mammakarzinom: Senken Statine das krebsbedingte Sterberisiko?

15.05.2024 Mammakarzinom Nachrichten

Frauen mit lokalem oder metastasiertem Brustkrebs, die Statine einnehmen, haben eine niedrigere krebsspezifische Mortalität als Patientinnen, die dies nicht tun, legen neue Daten aus den USA nahe.

Labor, CT-Anthropometrie zeigen Risiko für Pankreaskrebs

13.05.2024 Pankreaskarzinom Nachrichten

Gerade bei aggressiven Malignomen wie dem duktalen Adenokarzinom des Pankreas könnte Früherkennung die Therapiechancen verbessern. Noch jedoch klafft hier eine Lücke. Ein Studienteam hat einen Weg gesucht, sie zu schließen.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.