Skip to main content
Erschienen in: Clinical & Experimental Metastasis 4/2012

01.04.2012 | Research Paper

Downregulation of protein tyrosine phosphatase PTPL1 alters cell cycle and upregulates invasion-related genes in prostate cancer cells

verfasst von: Carolina Castilla, M. Luz Flores, José M. Conde, Rafael Medina, Francisco J. Torrubia, Miguel A. Japón, Carmen Sáez

Erschienen in: Clinical & Experimental Metastasis | Ausgabe 4/2012

Einloggen, um Zugang zu erhalten

Abstract

PTPL1, a non-receptor type protein tyrosine phosphatase, has been involved in the regulation of apoptosis and invasiveness of various tumour cell types, but its role in prostate cancer remained to be investigated. We report here that downregulation of PTPL1 by small interfering RNA in PC3 cells decreases cell proliferation and concomitantly reduces the expression of cell cycle-related proteins such as cyclins E and B1, PCNA, PTTG1 and phospho-histone H3. PTPL1 downregulation also increases the invasion ability of PC3 cells through Matrigel coated membranes. cDNA array of PTPL1-silenced PC3 cells versus control cells showed an upregulation of invasion-related genes such as uPA, uPAR, tPA, PAI-1, integrin α6 and osteopontin. This increased expression was also confirmed in PTPL1-silenced DU145 prostate cancer cells by quantitative real time PCR and western blot. These findings suggest that PTPL1 is an important mediator of central cellular processes such as proliferation and invasion.
Literatur
1.
2.
Zurück zum Zitat Morrissey C, Vessella RL (2007) The role of tumor microenvironment in prostate cancer bone metastasis. J Cell Biochem 101(4):873–886PubMedCrossRef Morrissey C, Vessella RL (2007) The role of tumor microenvironment in prostate cancer bone metastasis. J Cell Biochem 101(4):873–886PubMedCrossRef
3.
4.
Zurück zum Zitat Erdmann KS (2003) The protein tyrosine phosphatase PTP-basophil/basophil-like. Interacting proteins and molecular functions. Eur J Biochem 270(24):4789–4798PubMedCrossRef Erdmann KS (2003) The protein tyrosine phosphatase PTP-basophil/basophil-like. Interacting proteins and molecular functions. Eur J Biochem 270(24):4789–4798PubMedCrossRef
5.
Zurück zum Zitat Abaan OD, Toretsky JA (2008) PTPL1: a large phosphatase with a split personality. Cancer Metastasis Rev 27(2):205–214PubMedCrossRef Abaan OD, Toretsky JA (2008) PTPL1: a large phosphatase with a split personality. Cancer Metastasis Rev 27(2):205–214PubMedCrossRef
6.
Zurück zum Zitat Freiss G, Chalbos D (2011) PTPN13/PTPL1: an important regulator of tumor aggressiveness. Anticancer Agents Med Chem 11(1):78–88PubMed Freiss G, Chalbos D (2011) PTPN13/PTPL1: an important regulator of tumor aggressiveness. Anticancer Agents Med Chem 11(1):78–88PubMed
7.
Zurück zum Zitat Wang Z, Shen D, Parsons DW, Bardelli A, Sager J, Szabo S, Ptak J, Silliman N, Peters BA, van der Heijden MS, Parmigiani G, Yan H, Wang TL, Riggins G, Powell SM, Willson JK, Markowitz S, Kinzler KW, Vogelstein B, Velculescu VE (2004) Mutational analysis of the tyrosine phosphatome in colorectal cancers. Science 304(5674):1164–1166PubMedCrossRef Wang Z, Shen D, Parsons DW, Bardelli A, Sager J, Szabo S, Ptak J, Silliman N, Peters BA, van der Heijden MS, Parmigiani G, Yan H, Wang TL, Riggins G, Powell SM, Willson JK, Markowitz S, Kinzler KW, Vogelstein B, Velculescu VE (2004) Mutational analysis of the tyrosine phosphatome in colorectal cancers. Science 304(5674):1164–1166PubMedCrossRef
8.
Zurück zum Zitat Herrmann L, Dittmar T, Erdmann KS (2003) The protein tyrosine phosphatase PTP-BL associates with the midbody and is involved in the regulation of cytokinesis. Mol Biol Cell 14(1):230–240PubMedCrossRef Herrmann L, Dittmar T, Erdmann KS (2003) The protein tyrosine phosphatase PTP-BL associates with the midbody and is involved in the regulation of cytokinesis. Mol Biol Cell 14(1):230–240PubMedCrossRef
9.
Zurück zum Zitat Nedachi T, Conti M (2004) Potential role of protein tyrosine phosphatase nonreceptor type 13 in the control of oocyte meiotic maturation. Development 131(20):4987–4998PubMedCrossRef Nedachi T, Conti M (2004) Potential role of protein tyrosine phosphatase nonreceptor type 13 in the control of oocyte meiotic maturation. Development 131(20):4987–4998PubMedCrossRef
10.
Zurück zum Zitat Zhu JH, Chen R, Yi W, Cantin GT, Fearns C, Yang Y, Yates JR 3rd, Lee JD (2008) Protein tyrosine phosphatase PTPN13 negatively regulates Her2/ErbB2 malignant signalling. Oncogene 27(18):2525–2531PubMedCrossRef Zhu JH, Chen R, Yi W, Cantin GT, Fearns C, Yang Y, Yates JR 3rd, Lee JD (2008) Protein tyrosine phosphatase PTPN13 negatively regulates Her2/ErbB2 malignant signalling. Oncogene 27(18):2525–2531PubMedCrossRef
11.
Zurück zum Zitat Lai YJ, Lin WC, Lin FT (2007) PTPL1/FAP-1 negatively regulates TRIP6 function in lysophosphatidic acid-induced cell migration. J Biol Chem 282(33):24381–24387PubMedCrossRef Lai YJ, Lin WC, Lin FT (2007) PTPL1/FAP-1 negatively regulates TRIP6 function in lysophosphatidic acid-induced cell migration. J Biol Chem 282(33):24381–24387PubMedCrossRef
12.
Zurück zum Zitat Hoover AC, Strand GL, Nowicki PN, Anderson ME, Vermeer PD, Klingelhutz AJ, Bossler AD, Pottala JV, Hendriks WJ, Lee JH (2009) Impaired PTPN13 phosphatase activity in spontaneous or HPV-induced squamous cell carcinomas potentiates oncogene signaling through the MAP kinase pathway. Oncogene 28(45):3960–3970PubMedCrossRef Hoover AC, Strand GL, Nowicki PN, Anderson ME, Vermeer PD, Klingelhutz AJ, Bossler AD, Pottala JV, Hendriks WJ, Lee JH (2009) Impaired PTPN13 phosphatase activity in spontaneous or HPV-induced squamous cell carcinomas potentiates oncogene signaling through the MAP kinase pathway. Oncogene 28(45):3960–3970PubMedCrossRef
13.
Zurück zum Zitat Glondu-Lassis M, Dromard M, Lacroix-Triki M, Nirdé P, Puech C, Knani D, Chalbos D, Freiss G (2010) PTPL1/PTPN13 regulates breast cancer cell aggressiveness through direct inactivation of Src kinase. Cancer Res 70(12):5116–5126PubMedCrossRef Glondu-Lassis M, Dromard M, Lacroix-Triki M, Nirdé P, Puech C, Knani D, Chalbos D, Freiss G (2010) PTPL1/PTPN13 regulates breast cancer cell aggressiveness through direct inactivation of Src kinase. Cancer Res 70(12):5116–5126PubMedCrossRef
14.
Zurück zum Zitat Domínguez A, Ramos-Morales F, Romero F, Rios RM, Dreyfus F, Tortolero M, Pintor-Toro JA (1998) hpttg, a human homologue of rat pttg, is overexpressed in hematopoietic neoplasms. Evidence for a transcriptional activation function of hPTTG. Oncogene 17(17):2187–2193PubMedCrossRef Domínguez A, Ramos-Morales F, Romero F, Rios RM, Dreyfus F, Tortolero M, Pintor-Toro JA (1998) hpttg, a human homologue of rat pttg, is overexpressed in hematopoietic neoplasms. Evidence for a transcriptional activation function of hPTTG. Oncogene 17(17):2187–2193PubMedCrossRef
15.
Zurück zum Zitat Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29(9):e45PubMedCrossRef Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29(9):e45PubMedCrossRef
16.
Zurück zum Zitat Hiendlmeyer E, Regus S, Wassermann S, Hlubek F, Haynl A, Dimmler A, Koch C, Knoll C, van Beest M, Reuning U, Brabletz T, Kirchner T, Jung A (2004) Beta-catenin up-regulates the expression of the urokinase plasminogen activator in human colorectal tumors. Cancer Res 64(4):1209–1214PubMedCrossRef Hiendlmeyer E, Regus S, Wassermann S, Hlubek F, Haynl A, Dimmler A, Koch C, Knoll C, van Beest M, Reuning U, Brabletz T, Kirchner T, Jung A (2004) Beta-catenin up-regulates the expression of the urokinase plasminogen activator in human colorectal tumors. Cancer Res 64(4):1209–1214PubMedCrossRef
17.
Zurück zum Zitat Wang Q, Sun ZX, Allgayer H, Yang HS (2010) Downregulation of E-cadherin is an essential event in activating beta-catenin/Tcf-dependent transcription and expression of its target genes in Pdcd4 knockdown cells. Oncogene 29(1):128–138PubMedCrossRef Wang Q, Sun ZX, Allgayer H, Yang HS (2010) Downregulation of E-cadherin is an essential event in activating beta-catenin/Tcf-dependent transcription and expression of its target genes in Pdcd4 knockdown cells. Oncogene 29(1):128–138PubMedCrossRef
18.
Zurück zum Zitat Malumbres M, Barbacid M (2009) Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer 9(3):153–166PubMedCrossRef Malumbres M, Barbacid M (2009) Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer 9(3):153–166PubMedCrossRef
19.
Zurück zum Zitat Maga G, Hubscher U (2003) Proliferating cell nuclear antigen (PCNA): a dancer with many partners. J Cell Sci 116(Pt 15):3051–3060PubMedCrossRef Maga G, Hubscher U (2003) Proliferating cell nuclear antigen (PCNA): a dancer with many partners. J Cell Sci 116(Pt 15):3051–3060PubMedCrossRef
20.
Zurück zum Zitat Ramos-Morales F, Domínguez A, Romero F, Luna R, Multon MC, Pintor-Toro JA, Tortolero M (2000) Cell cycle regulated expression and phosphorylation of hpttg proto-oncogene product. Oncogene 19(3):403–409PubMedCrossRef Ramos-Morales F, Domínguez A, Romero F, Luna R, Multon MC, Pintor-Toro JA, Tortolero M (2000) Cell cycle regulated expression and phosphorylation of hpttg proto-oncogene product. Oncogene 19(3):403–409PubMedCrossRef
21.
Zurück zum Zitat Hayashi-Takanaka Y, Yamagata K, Nozaki N, Kimura H (2009) Visualizing histone modifications in living cells: spatiotemporal dynamics of H3 phosphorylation during interphase. J Cell Biol 187(6):781–790PubMedCrossRef Hayashi-Takanaka Y, Yamagata K, Nozaki N, Kimura H (2009) Visualizing histone modifications in living cells: spatiotemporal dynamics of H3 phosphorylation during interphase. J Cell Biol 187(6):781–790PubMedCrossRef
22.
Zurück zum Zitat Andreasen PA, Egelund R, Petersen HH (2000) The plasminogen activation system in tumor growth, invasion, and metastasis. Cell Mol Life Sci 57(1):25–40PubMedCrossRef Andreasen PA, Egelund R, Petersen HH (2000) The plasminogen activation system in tumor growth, invasion, and metastasis. Cell Mol Life Sci 57(1):25–40PubMedCrossRef
23.
Zurück zum Zitat Duffy MJ (2002) Urokinase plasminogen activator and its inhibitor, PAI-1, as prognostic markers in breast cancer: from pilot to level 1 evidence studies. Clin Chem 48(8):1194–1197PubMed Duffy MJ (2002) Urokinase plasminogen activator and its inhibitor, PAI-1, as prognostic markers in breast cancer: from pilot to level 1 evidence studies. Clin Chem 48(8):1194–1197PubMed
24.
Zurück zum Zitat Werle B, Kotzsch M, Lah TT, Kos J, Gabrijelcic-Geiger D, Spiess E, Schirren J, Ebert W, Fiehn W, Luther T, Magdolen V, Schmitt M, Harbeck N (2004) Cathepsin B, plasminogen activator inhibitor (PAI-1) and plasminogen activator-receptor (uPAR) are prognostic factors for patients with non-small cell lung cancer. Anticancer Res 24(6):4147–4161PubMed Werle B, Kotzsch M, Lah TT, Kos J, Gabrijelcic-Geiger D, Spiess E, Schirren J, Ebert W, Fiehn W, Luther T, Magdolen V, Schmitt M, Harbeck N (2004) Cathepsin B, plasminogen activator inhibitor (PAI-1) and plasminogen activator-receptor (uPAR) are prognostic factors for patients with non-small cell lung cancer. Anticancer Res 24(6):4147–4161PubMed
25.
Zurück zum Zitat Dong Z, Saliganan AD, Meng H, Nabha SM, Sabbota AL, Sheng S, Bonfil RD, Cher ML (2008) Prostate cancer cell-derived urokinase-type plasminogen activator contributes to intraosseous tumor growth and bone turnover. Neoplasia 10(5):439–449PubMed Dong Z, Saliganan AD, Meng H, Nabha SM, Sabbota AL, Sheng S, Bonfil RD, Cher ML (2008) Prostate cancer cell-derived urokinase-type plasminogen activator contributes to intraosseous tumor growth and bone turnover. Neoplasia 10(5):439–449PubMed
26.
Zurück zum Zitat Gupta A, Lotan Y, Ashfaq R, Roehrborn CG, Raj GV, Aragaki CC, Montorsi F, Shariat SF (2009) Predictive value of the differential expression of the urokinase plasminogen activation axis in radical prostatectomy patients. Eur Urol 55(5):1124–1133PubMedCrossRef Gupta A, Lotan Y, Ashfaq R, Roehrborn CG, Raj GV, Aragaki CC, Montorsi F, Shariat SF (2009) Predictive value of the differential expression of the urokinase plasminogen activation axis in radical prostatectomy patients. Eur Urol 55(5):1124–1133PubMedCrossRef
27.
Zurück zum Zitat Pulukuri SM, Gondi CS, Lakka SS, Jutla A, Estes N, Gujrati M, Rao JS (2005) RNA interference-directed knockdown of urokinase plasminogen activator and urokinase plasminogen activator receptor inhibits prostate cancer cell invasion, survival, and tumorigenicity in vivo. J Biol Chem 280(43):36529–36540PubMedCrossRef Pulukuri SM, Gondi CS, Lakka SS, Jutla A, Estes N, Gujrati M, Rao JS (2005) RNA interference-directed knockdown of urokinase plasminogen activator and urokinase plasminogen activator receptor inhibits prostate cancer cell invasion, survival, and tumorigenicity in vivo. J Biol Chem 280(43):36529–36540PubMedCrossRef
28.
Zurück zum Zitat Rabinovitz I, Nagle RB, Cress AE (1995) Integrin alpha 6 expression in human prostate carcinoma cells is associated with a migratory and invasive phenotype in vitro and in vivo. Clin Exp Metastasis 13(6):481–491PubMedCrossRef Rabinovitz I, Nagle RB, Cress AE (1995) Integrin alpha 6 expression in human prostate carcinoma cells is associated with a migratory and invasive phenotype in vitro and in vivo. Clin Exp Metastasis 13(6):481–491PubMedCrossRef
29.
Zurück zum Zitat Schmelz M, Cress AE, Scott KM, Burger F, Cui H, Sallam K, McDaniel KM, Dalkin BL, Nagle RB (2002) Different phenotypes in human prostate cancer: alpha6 or alpha3 integrin in cell-extracellular adhesion sites. Neoplasia 4(3):243–254PubMedCrossRef Schmelz M, Cress AE, Scott KM, Burger F, Cui H, Sallam K, McDaniel KM, Dalkin BL, Nagle RB (2002) Different phenotypes in human prostate cancer: alpha6 or alpha3 integrin in cell-extracellular adhesion sites. Neoplasia 4(3):243–254PubMedCrossRef
30.
Zurück zum Zitat Pawar SC, Demetriou MC, Nagle RB, Bowden GT, Cress AE (2007) Integrin alpha6 cleavage: a novel modification to modulate cell migration. Exp Cell Res 313(6):1080–1089PubMedCrossRef Pawar SC, Demetriou MC, Nagle RB, Bowden GT, Cress AE (2007) Integrin alpha6 cleavage: a novel modification to modulate cell migration. Exp Cell Res 313(6):1080–1089PubMedCrossRef
31.
Zurück zum Zitat Ports MO, Nagle RB, Pond GD, Cress AE (2009) Extracellular engagement of alpha6 integrin inhibited urokinase-type plasminogen activator-mediated cleavage and delayed human prostate bone metastasis. Cancer Res 69(12):5007–5014PubMedCrossRef Ports MO, Nagle RB, Pond GD, Cress AE (2009) Extracellular engagement of alpha6 integrin inhibited urokinase-type plasminogen activator-mediated cleavage and delayed human prostate bone metastasis. Cancer Res 69(12):5007–5014PubMedCrossRef
32.
Zurück zum Zitat Rangaswami H, Bulbule A, Kundu GC (2006) Osteopontin: role in cell signaling and cancer progression. Trends Cell Biol 16(2):79–87PubMedCrossRef Rangaswami H, Bulbule A, Kundu GC (2006) Osteopontin: role in cell signaling and cancer progression. Trends Cell Biol 16(2):79–87PubMedCrossRef
33.
Zurück zum Zitat Forootan SS, Foster CS, Aachi VR, Adamson J, Smith PH, Lin K, Ke Y (2006) Prognostic significance of osteopontin expression in human prostate cancer. Int J Cancer 118(9):2255–2261PubMedCrossRef Forootan SS, Foster CS, Aachi VR, Adamson J, Smith PH, Lin K, Ke Y (2006) Prognostic significance of osteopontin expression in human prostate cancer. Int J Cancer 118(9):2255–2261PubMedCrossRef
34.
Zurück zum Zitat Caruso DJ, Carmack AJ, Lokeshwar VB, Duncan RC, Soloway MS, Lokeshwar BL (2008) Osteopontin and interleukin-8 expression is independently associated with prostate cancer recurrence. Clin Cancer Res 14(13):4111–4118PubMedCrossRef Caruso DJ, Carmack AJ, Lokeshwar VB, Duncan RC, Soloway MS, Lokeshwar BL (2008) Osteopontin and interleukin-8 expression is independently associated with prostate cancer recurrence. Clin Cancer Res 14(13):4111–4118PubMedCrossRef
35.
Zurück zum Zitat Das R, Mahabeleshwar GH, Kundu GC (2004) Osteopontin induces AP-1-mediated secretion of urokinase-type plasminogen activator through c-Src-dependent epidermal growth factor receptor transactivation in breast cancer cells. J Biol Chem 279(12):11051–11064PubMedCrossRef Das R, Mahabeleshwar GH, Kundu GC (2004) Osteopontin induces AP-1-mediated secretion of urokinase-type plasminogen activator through c-Src-dependent epidermal growth factor receptor transactivation in breast cancer cells. J Biol Chem 279(12):11051–11064PubMedCrossRef
36.
Zurück zum Zitat Erdmann KS, Kuhlmann J, Lessmann V, Herrmann L, Eulenburg V, Müller O, Heumann R (2000) The adenomatous polyposis coli-protein (APC) interacts with the protein tyrosine phosphatase PTP-BL via an alternatively spliced PDZ domain. Oncogene 19(34):3894–3901PubMedCrossRef Erdmann KS, Kuhlmann J, Lessmann V, Herrmann L, Eulenburg V, Müller O, Heumann R (2000) The adenomatous polyposis coli-protein (APC) interacts with the protein tyrosine phosphatase PTP-BL via an alternatively spliced PDZ domain. Oncogene 19(34):3894–3901PubMedCrossRef
Metadaten
Titel
Downregulation of protein tyrosine phosphatase PTPL1 alters cell cycle and upregulates invasion-related genes in prostate cancer cells
verfasst von
Carolina Castilla
M. Luz Flores
José M. Conde
Rafael Medina
Francisco J. Torrubia
Miguel A. Japón
Carmen Sáez
Publikationsdatum
01.04.2012
Verlag
Springer Netherlands
Erschienen in
Clinical & Experimental Metastasis / Ausgabe 4/2012
Print ISSN: 0262-0898
Elektronische ISSN: 1573-7276
DOI
https://doi.org/10.1007/s10585-012-9455-7

Weitere Artikel der Ausgabe 4/2012

Clinical & Experimental Metastasis 4/2012 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.