Serine/Threonine Protein Phosphatase-5 Accelerates Cell Growth and Migration in Human Glioma
- 308 Downloads
Glioma is the most common type of primary central nervous system tumor. Ser/Thr protein phosphatase 5 (PP5) has been shown to regulate multiple signaling cascades that suppress growth and facilitate apoptosis in several human cancer cells. However, the role of PP5 in human gliomas remains unclear. Herein, the relationship between PP5 expression and glioma cell growth was investigated, and the therapeutic value of PP5 in glioma was further evaluated. We employed a short hairpin RNA targeting PPP5C gene to knock down PP5 expression in human glioma cell lines U251 and U373. Depletion of PPP5C via RNAi remarkably inhibited glioma cell proliferation and colony formation, and arrested cell cycle in the G0/G1 phase. Moreover, knockdown of PP5 markedly suppressed glioma cell migration, as determined by Transwell assay. Our findings suggest that PPP5C could be essential for glioma cell growth and serve as a promising therapeutic target in human gliomas.
KeywordsGlioma PPP5C Proliferation Migration
Conflict of interest
The authors declare that they have no conflict of interest.
- Ghobrial IM, McCormick DJ, Kaufmann SH, Leontovich AA, Loegering DA, Dai NT, Krajnik KL, Stenson MJ, Melhem MF, Novak AJ, Ansell SM, Witzig TE (2005) Proteomic analysis of mantle-cell lymphoma by protein microarray. Blood 105(9):3722–3730. doi: 10.1182/blood-2004-10-3999 PubMedCentralPubMedCrossRefGoogle Scholar
- Golden T, Aragon IV, Rutland B, Tucker JA, Shevde LA, Samant RS, Zhou G, Amable L, Skarra D, Honkanen RE (2008a) Elevated levels of Ser/Thr protein phosphatase 5 (PP5) in human breast cancer. Biochim Biophys Acta 1782(4):259–270. doi: 10.1016/j.bbadis.2008.01.004 PubMedCentralPubMedCrossRefGoogle Scholar
- Huang S, Shu L, Easton J, Harwood FC, Germain GS, Ichijo H, Houghton PJ (2004) Inhibition of mammalian target of rapamycin activates apoptosis signal-regulating kinase 1 signaling by suppressing protein phosphatase 5 activity. J Biol Chem 279(35):36490–36496. doi: 10.1074/jbc.M401208200 PubMedCrossRefGoogle Scholar
- Matsuzawa A, Nishitoh H, Tobiume K, Takeda K, Ichijo H (2002) Physiological roles of ASK1-mediated signal transduction in oxidative stress- and endoplasmic reticulum stress-induced apoptosis: advanced findings from ASK1 knockout mice. Antioxid Redox Signal 4(3):415–425. doi: 10.1089/15230860260196218 PubMedCrossRefGoogle Scholar
- Mkaddem SB, Werts C, Goujon JM, Bens M, Pedruzzi E, Ogier-Denis E, Vandewalle A (2009) Heat shock protein gp96 interacts with protein phosphatase 5 and controls toll-like receptor 2 (TLR2)-mediated activation of extracellular signal-regulated kinase (ERK) 1/2 in post-hypoxic kidney cells. J Biol Chem 284(18):12541–12549. doi: 10.1074/jbc.M808376200 PubMedCentralPubMedCrossRefGoogle Scholar
- Ostrom QT, Gittleman H, Farah P, Ondracek A, Chen Y, Wolinsky Y, Stroup NE, Kruchko C, Barnholtz-Sloan JS (2013) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2006–2010. Neuro Oncol 15(Suppl 2):ii1–ii56. doi: 10.1093/neuonc/not151 PubMedCentralPubMedCrossRefGoogle Scholar
- Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO, European Organisation for R, Treatment of Cancer Brain T, Radiotherapy G, National Cancer Institute of Canada Clinical Trials G (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10):987–996. doi: 10.1056/NEJMoa043330 PubMedCrossRefGoogle Scholar
- Vaughan CK, Mollapour M, Smith JR, Truman A, Hu B, Good VM, Panaretou B, Neckers L, Clarke PA, Workman P, Piper PW, Prodromou C, Pearl LH (2008) Hsp90-dependent activation of protein kinases is regulated by chaperone-targeted dephosphorylation of Cdc37. Mol Cell 31(6):886–895. doi: 10.1016/j.molcel.2008.07.021 PubMedCentralPubMedCrossRefGoogle Scholar