PPP5c promotes cell proliferation and survival in human prostate cancer by regulating of the JnK and erK1/2 phosphorylation

is one of the most common malignancies and a major leading cause of cancer-related deaths in males. And it is necessary to explore new molecular targets to enhance diagnosis and treatment level of the PCa. Serine/threonine protein phosphatase 5 (PPP5C) is a vital molecule that Involve in complex cell physiological activity. Purpose: The objective of this study was to detecte the expression level of PPP5C in the tissue of prostate cancer patients and further discussed the PPP5C biological function and mechanisms on the PCa. Methods: The expression level of PPP5C was analyzed by immunohistochemistry and ONCOMINE datasets. Lentivirus-mediated short hairpin RNA (shRNA) was constructed to silence the expression of PPP5C in prostate cancer cell. Cell viability and proliferation were measured using MTT and colony formation, and the cell cycle and apoptosis was analyszed by flow cytometry. The changes of downstream protein level and protein phosphorylation level were detected by western blot. Results: PPP5C was highly expressed in PCa tissue as analyzed by immunohistochemistry and ONCOMINE datasets. PPP5C Knockdown inhibited cell proliferation and colony formation in PCa cells. Flow cytometry analysis showed that DU145, PC3 and 22RV1 PCa cells deprived of PPP5C were arrested in G0/G1 phase and became apoptotic. Western blot analysis indicated that PPP5C knockdown could promote JNK and ERK phosphorylation. Conclusion: Our study indicated that the PPP5C may become a new potential diagnostic biomarker and therapeutic target for the PCa. that of the indicated that the new potential diagnostic biomarker and therapeutic target for the PCa.

[1]  Manjulika Das.  Androgen deprivation therapy for prostate cancer. , 2017, The Lancet. Oncology.

[2]  Shile Huang,et al.  Resveratrol prevents cadmium activation of Erk1/2 and JNK pathways from neuronal cell death via protein phosphatases 2A and 5 , 2015, Journal of neurochemistry.

[3]  Hua Yu,et al.  Inhibition of protein phosphatase 5 (PP5) suppresses survival and growth of colorectal cancer cells , 2015, Biotechnology and applied biochemistry.

[4]  Hongqi Zhang,et al.  Serine/Threonine Protein Phosphatase-5 Accelerates Cell Growth and Migration in Human Glioma , 2015, Cellular and Molecular Neurobiology.

[5]  A. Kural,et al.  Prostate cancer in Asia: A collaborative report , 2014, Asian journal of urology.

[6]  Y. Odaka,et al.  Curcumin inhibits protein phosphatases 2A and 5, leading to activation of mitogen-activated protein kinases and death in tumor cells. , 2012, Carcinogenesis.

[7]  G. Pirianov,et al.  Involvement of stress activated protein kinases (JNK and p38) in 1,25 dihydroxyvitamin D3-induced breast cell death , 2010, Steroids.

[8]  C. Chien,et al.  Novel indoloquinoline derivative, IQDMA, induces G(2)/M phase arrest and apoptosis in A549 cells through JNK/p38 MAPK signaling activation. , 2009, Life sciences.

[9]  E. Wagner,et al.  Signal integration by JNK and p38 MAPK pathways in cancer development , 2009, Nature Reviews Cancer.

[10]  Bruce Montgomery,et al.  Androgen deprivation therapy: progress in understanding mechanisms of resistance and optimizing androgen depletion , 2009, Nature Clinical Practice Urology.

[11]  L. Pearl,et al.  Hsp90-Dependent Activation of Protein Kinases Is Regulated by Chaperone-Targeted Dephosphorylation of Cdc37 , 2008, Molecular cell.

[12]  R. Samant,et al.  Elevated levels of Ser/Thr protein phosphatase 5 (PP5) in human breast cancer. , 2008, Biochimica et biophysica acta.

[13]  R. Honkanen,et al.  The role of serine/threonine protein phosphatase type 5 (PP5) in the regulation of stress-induced signaling networks and cancer , 2008, Cancer and Metastasis Reviews.

[14]  Suzanne Schubbert,et al.  Hyperactive Ras in developmental disorders and cancer , 2007, Nature Reviews Cancer.

[15]  Hui-Hsuan Lin,et al.  Chemopreventive properties of Hibiscus sabdariffa L. on human gastric carcinoma cells through apoptosis induction and JNK/p38 MAPK signaling activation. , 2007, Chemico-biological interactions.

[16]  B. H. Shah,et al.  Protein phosphatase 5 as a negative key regulator of Raf-1 activation , 2006, Trends in Endocrinology & Metabolism.

[17]  R. Dickinson,et al.  Diverse physiological functions for dual-specificity MAP kinase phosphatases , 2006, Journal of Cell Science.

[18]  Laura M. Heiser,et al.  Regulation of the Raf–MEK–ERK pathway by protein phosphatase 5 , 2006, Nature Cell Biology.

[19]  E. Wallen,et al.  Characterization of Biochemical Recurrence after Radical Prostatectomy , 2006, Urologia Internationalis.

[20]  Xiao-Fan Wang,et al.  Protein Phosphatase 5 Is Required for ATR-Mediated Checkpoint Activation , 2005, Molecular and Cellular Biology.

[21]  D. Loegering,et al.  Proteomic analysis of mantle-cell lymphoma by protein microarray. , 2005, Blood.

[22]  P. Hu,et al.  Critical Role of Endogenous Akt/IAPs and MEK1/ERK Pathways in Counteracting Endoplasmic Reticulum Stress-induced Cell Death* , 2004, Journal of Biological Chemistry.

[23]  Guofei Zhou,et al.  Ser/Thr Protein Phosphatase 5 Inactivates Hypoxia-induced Activation of an Apoptosis Signal-regulating Kinase 1/MKK-4/JNK Signaling Cascade* , 2004, Journal of Biological Chemistry.

[24]  William J Catalona,et al.  Cancer progression and survival rates following anatomical radical retropubic prostatectomy in 3,478 consecutive patients: long-term results. , 2004, The Journal of urology.

[25]  K. Arai,et al.  Involvement of ERK MAP kinase in endoplasmic reticulum stress in SH‐SY5Y human neuroblastoma cells , 2004, Journal of neurochemistry.

[26]  David J. Chen,et al.  DNA-PKcs function regulated specifically by protein phosphatase 5. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[27]  Xiao-Fan Wang,et al.  Requirement of protein phosphatase 5 in DNA-damage-induced ATM activation. , 2004, Genes & development.

[28]  Jung-Min Park,et al.  Characterization of Saccharomyces cerevisiae protein Ser/Thr phosphatase T1 and comparison to its mammalian homolog PP5 , 2003, BMC Cell Biology.

[29]  T. Mak,et al.  ERK Activation Mediates Cell Cycle Arrest and Apoptosis after DNA Damage Independently of p53* , 2002, The Journal of Biological Chemistry.

[30]  H. Ichijo,et al.  Negative feedback regulation of ASK1 by protein phosphatase 5 (PP5) in response to oxidative stress , 2001, The EMBO journal.

[31]  Y. Yarden,et al.  Taxol-induced apoptosis depends on MAP kinase pathways (ERK and p38) and is independent of p53 , 2001, Oncogene.

[32]  Y. Matsuda,et al.  Expression in hepatomas and chromosomal localization of rat protein phosphatase 5 gene. , 2000, International journal of oncology.

[33]  N. Dean,et al.  Serine/Threonine Protein Phosphatase Type 5 Acts Upstream of p53 to Regulate the Induction of p21WAF1/Cip1 and Mediate Growth Arrest* , 1998, The Journal of Biological Chemistry.

[34]  A. Silverstein,et al.  The Tetratricopeptide Repeat Domain of Protein Phosphatase 5 Mediates Binding to Glucocorticoid Receptor Heterocomplexes and Acts as a Dominant Negative Mutant* , 1996, The Journal of Biological Chemistry.

[35]  A. Zetterberg,et al.  Chromosomal localization and 5' sequence of the human protein serine/threonine phosphatase 5' gene. , 1996, Biochemical and Biophysical Research Communications - BBRC.

[36]  Xiaojiao Zheng,et al.  Knockdown of protein phosphatase 5 inhibits ovarian cancer growth in vitro. , 2016, Oncology letters.

[37]  Ming Liu,et al.  Knockdown of PPP5C Inhibits Growth of Hepatocellular Carcinoma Cells In Vitro , 2014, Applied Biochemistry and Biotechnology.

[38]  A. Jemal,et al.  Global cancer statistics , 2011, CA: a cancer journal for clinicians.

[39]  A. Nairn,et al.  Protein phosphatases: recent progress. , 1991, Advances in second messenger and phosphoprotein research.