The Oncogenic Protein Kinase/ATPase RIOK1 Is Up-Regulated via the c-myc/E2F Transcription Factor Axis in Prostate Cancer

Abstract

The atypical protein kinase/ATPase RIO kinase (RIOK)-1 is involved in pre-40S ribosomal subunit production, cell-cycle progression, and protein arginine N-methyltransferase 5 methylosome substrate recruitment. RIOK1 overexpression is a characteristic of several malignancies and has been correlated with cancer stage, therapy resistance, poor patient survival, and other prognostic factors, but its role in prostate cancer (PCa) is unknown. In this study, the expression, regulation, and therapeutic potential of RIOK1 in PCa were examined. RIOK1 mRNA and protein expression were elevated in PCa tissue samples and correlated with proliferative and protein homeostasis related pathways. RIOK1 was identified as a downstream target gene of the c-myc/E2F transcription factors. Proliferation of PCa cells was significantly reduced with RIOK1 knockdown and overexpression of the dominant-negative RIOK1-D324A mutant. Biochemical inhibition of RIOK1 with toyocamycin led to strong antiproliferative effects in androgen receptor–negative and –positive PCa cell lines with EC50 values of 3.5 to 8.8 nmol/L. Rapid decreases in RIOK1 protein expression and total rRNA content, and a shift in the 28S/18S rRNA ratio, were found with toyocamycin treatment. Apoptosis was induced with toyocamycin treatment at a level similar to that with the chemotherapeutic drug docetaxel used in clinical practice. In summary, RIOK1 is a part of the MYC oncogene network, and as such, could be considered for future treatment of patients with PCa. The atypical protein kinase/ATPase RIO kinase (RIOK)-1 is involved in pre-40S ribosomal subunit production, cell-cycle progression, and protein arginine N-methyltransferase 5 methylosome substrate recruitment. RIOK1 overexpression is a characteristic of several malignancies and has been correlated with cancer stage, therapy resistance, poor patient survival, and other prognostic factors, but its role in prostate cancer (PCa) is unknown. In this study, the expression, regulation, and therapeutic potential of RIOK1 in PCa were examined. RIOK1 mRNA and protein expression were elevated in PCa tissue samples and correlated with proliferative and protein homeostasis related pathways. RIOK1 was identified as a downstream target gene of the c-myc/E2F transcription factors. Proliferation of PCa cells was significantly reduced with RIOK1 knockdown and overexpression of the dominant-negative RIOK1-D324A mutant. Biochemical inhibition of RIOK1 with toyocamycin led to strong antiproliferative effects in androgen receptor–negative and –positive PCa cell lines with EC50 values of 3.5 to 8.8 nmol/L. Rapid decreases in RIOK1 protein expression and total rRNA content, and a shift in the 28S/18S rRNA ratio, were found with toyocamycin treatment. Apoptosis was induced with toyocamycin treatment at a level similar to that with the chemotherapeutic drug docetaxel used in clinical practice. In summary, RIOK1 is a part of the MYC oncogene network, and as such, could be considered for future treatment of patients with PCa. Prostate cancer (PCa) is among the most frequently diagnosed cancers in men, with nearly 1.5 million new cases recognized worldwide per year.1Sung H. Ferlay J. Siegel R.L. Laversanne M. Soerjomataram I. Jemal A. Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J Clin. 2021; 71: 209-249Crossref PubMed Scopus (31844) Google Scholar PCa can be cured by radical prostatectomy and radiation therapy when detected in the early stages.2Mottet N. van den Bergh R.C.N. Briers E. Van den Broeck T. Cumberbatch M.G. De Santis M. Fanti S. Fossati N. Gandaglia G. Gillessen S. Grivas N. Grummet J. Henry A.M. van der Kwast T.H. Lam T.B. Lardas M. Liew M. Mason M.D. Moris L. Oprea-Lager D.E. van der Poel H.G. Rouviere O. Schoots I.G. Tilki D. Wiegel T. Willemse P.M. Cornford P. EAU-EANM-ESTRO-ESUR-SIOG guidelines on prostate cancer-2020 update. Part 1: screening, diagnosis, and local treatment with curative intent.Eur Urol. 2021; 79: 243-262Abstract Full Text Full Text PDF PubMed Scopus (969) Google Scholar Several new androgen receptor (AR)–signaling inhibitors, poly–ADP ribose polymerase (PARP) inhibitors, and radio ligand therapies have been approved for the treatment of patients with advanced PCa.3Wang B.R. Chen Y.A. Kao W.H. Lai C.H. Lin H. Hsieh J.T. Developing new treatment options for castration-resistant prostate cancer and recurrent disease.Biomedicines. 2022; 10: 1872Crossref PubMed Scopus (5) Google Scholar However, curative treatment of patients with advanced PCa remains elusive, and all currently available treatment regimens eventually lead to the development of therapy resistance. This demonstrates the urgent need for the identification of novel drug targets to expand the therapeutic opportunities for patients with advanced PCa. It is well known that protein kinases have a pivotal role in cancer initiation and progression. Consequently, >50 clinically approved kinase inhibitors have been made commercially available.4Kanev G.K. de Graaf C. de Esch I.J.P. Leurs R. Wurdinger T. Westerman B.A. Kooistra A.J. The landscape of atypical and eukaryotic protein kinases.Trends Pharmacol Sci. 2019; 40: 818-832Abstract Full Text Full Text PDF PubMed Google Scholar Several clinical trials of the efficacy of protein kinase inhibitors in the treatment of PCa are ongoing, but have not yet led to clinical approval.5Chau V. Madan R.A. Aragon-Ching J.B. Protein kinase inhibitors for the treatment of prostate cancer.Expert Opin Pharmacother. 2021; 22: 1889-1899Crossref PubMed Scopus (3) Google Scholar Thus, it is important to investigate still-unexplored protein kinases that promote PCa. Atypical protein kinases do not share clear sequence similarity with conventional kinases but still have protein kinase activity.4Kanev G.K. de Graaf C. de Esch I.J.P. Leurs R. Wurdinger T. Westerman B.A. Kooistra A.J. The landscape of atypical and eukaryotic protein kinases.Trends Pharmacol Sci. 2019; 40: 818-832Abstract Full Text Full Text PDF PubMed Google Scholar RIO kinase (RIOK)-1 is an atypical protein kinase/ATPase that has recently attracted significant interest in the cancer-research community due to its role in several important cellular processes. RIOK1 is involved in the final steps of pre-40S ribosomal maturation, cell-cycle progression, and protein arginine N-methyltransferase (PRMT)-5 methylosome substrate recruitment.6Ameismeier M. Zemp I. van den Heuvel J. Thoms M. Berninghausen O. Kutay U. Beckmann R. Structural basis for the final steps of human 40S ribosome maturation.Nature. 2020; 587: 683-687Crossref PubMed Scopus (34) Google Scholar, 7Berto G. Ferreira-Cerca S. De Wulf P. The Rio1 protein kinases/ATPases: conserved regulators of growth, division, and genomic stability.Curr Genet. 2019; 65: 457-466Crossref PubMed Scopus (8) Google Scholar, 8Mulvaney K.M. Blomquist C. Acharya N. Li R. Ranaghan M.J. O'Keefe M. Rodriguez D.J. Young M.J. Kesar D. Pal D. Stokes M. Nelson A.J. Jain S.S. Yang A. Mullin-Bernstein J. A. D. S. D. A.J. A. basis for substrate to the 2021; Full Text Full Text PDF PubMed Scopus Google Scholar have that RIOK1 is in cancer J. T. A.J. A.J. L. V. Cancer H. clinical to Full Text Full Text PDF PubMed Scopus Google Scholar and cancers as well as H. H. J. J. R. Li H. of RIOK1 the of and Scopus Google Scholar, Li S. D. H. M. of RIOK1 and as a prognostic in 2021; PubMed Scopus Google Scholar, R. S. RIOK1 is with cell cancer clinical and to cancer 2022; PubMed Scopus Google Scholar, Li T. C. C. expression of RIOK1 is correlated with cancer receptor and cancer 2020; Google Scholar In RIOK1 overexpression has been correlated with stage, therapy resistance, poor survival, and other prognostic in H. H. J. J. R. Li H. of RIOK1 the of and Scopus Google Scholar, Li S. D. H. M. of RIOK1 and as a prognostic in 2021; PubMed Scopus Google Scholar, R. S. RIOK1 is with cell cancer clinical and to cancer 2022; PubMed Scopus Google Scholar, Li T. C. C. expression of RIOK1 is correlated with cancer receptor and cancer 2020; Google Scholar, F. N. L. S. J. M. S. N. T. N. F. A. S. J. R. T. The atypical kinase RIOK1 and Full Text Full Text PDF PubMed Scopus Google Scholar, S. L. C. H. J. J. RIOK1 and in cancer of 2022; PubMed Scopus (3) Google Scholar In knockdown of RIOK1 led to in and in a of cancer cell Li S. D. H. M. of RIOK1 and as a prognostic in 2021; PubMed Scopus Google R. S. RIOK1 is with cell cancer clinical and to cancer 2022; PubMed Scopus Google F. N. L. S. J. M. S. N. T. N. F. A. S. J. R. T. The atypical kinase RIOK1 and Full Text Full Text PDF PubMed Scopus Google Scholar and F. N. L. S. J. M. S. N. T. N. F. A. S. J. R. T. The atypical kinase RIOK1 and Full Text Full Text PDF PubMed Scopus Google Scholar RIOK1 knockdown was to and the ribosomal protein ribosomal in J. I. A. Yang H. J.B. in that the RIO kinases cell and in Genet. PubMed Scopus Google Scholar RIOK1 was found to protein in cancer S. L. C. H. J. J. RIOK1 and in cancer of 2022; PubMed Scopus (3) Google Scholar However, the role of RIOK1 in prostate has not yet been In this study, the expression, regulation, and therapeutic potential of RIOK1 in PCa were and cells were in and cells were in The were with and cells were by and for for cells were with cells the were by and was with knockdown were by of at with and and overexpression was in cells by of at with knockdown was by of cells with a N. D. H. M. for in human 2020; PubMed Scopus Google Scholar and the expression M. C. A. D.E. F. for with PubMed Scopus Google and Biochemical inhibition of RIOK1 was by treatment of the cells with toyocamycin was used as a for Protein was by in and Protein was with was on to and to and were in in The were RIOK1 and and were an and Protein expression was to was in the with The and were used to samples for on a was The of the and were used for The were and RIOK1 was in the with The level was with the at the of the at the of the The cell was with a cell of the was in the were in in and with in The of cells was on and were with a of toyocamycin for The on cell was by on a 5 in for at EC50 values were in the were cell per well was and with and the was in the with was on a and to the cell was in the of rRNA were on a the were available were the S. T. P. M. M.J. of prostate cancer with gene expression in and PubMed Scopus Google Scholar N. H. A. P. E. N. T. I. M. A. C. genomic of human prostate Full Text Full Text PDF PubMed Scopus Google Scholar M.J. J. L. M. R. N. F. A.M. The landscape of castration-resistant prostate PubMed Scopus Google Scholar and I. G. A. J. S. S. A. H. G. A. S. A. M. C. A. J. S. S. H. D. A. of the prostate as a novel therapeutic target in prostate 2022; PubMed Scopus Google The Cancer Prostate J. T. A.J. A.J. L. V. Cancer H. clinical to Full Text Full Text PDF PubMed Scopus Google Scholar were the castration-resistant PCa J. G. D. J. I. of clinical in advanced prostate A. 2019; PubMed Scopus Google Scholar were the by the C. I. E. H. E. van der D. A. H. P. M.J. A. F. of in 2021; PubMed Scopus Google Scholar were the was in gene expression was with the and gene The was used for the the of the were with the and to of cells was as I. G. A. J. S. S. A. H. G. A. S. A. M. C. A. J. S. S. H. D. A. of the prostate as a novel therapeutic target in prostate 2022; PubMed Scopus Google Scholar gene expression was with expression was with was with to per The was used for and the and and transcription by the I. Lam P. J. Lin C. O. P. E. on the of 2020; PubMed Scopus Google Scholar were in the of The of tissue the PCa was approved by the of the of was all patients in with In this study, and cancer tissue patients and tissue and cancer tissue PCa patients radical prostatectomy were used to RIOK1 protein was the RIOK1 at a final of were with a with a were the was to The of cells was to were to an was in the and the expression of RIOK1 in a available of and tissue samples patients radical were I. G. A. J. S. S. A. H. G. A. S. A. M. C. A. J. S. S. H. D. A. of the prostate as a novel therapeutic target in prostate 2022; PubMed Scopus Google Scholar was and the and was but was of cell RIOK1 was in all cell and RIOK1 expression in The on were not due to by the cell in this The expression of RIOK1 mRNA was in the to the PCa In the in RIOK1 mRNA expression was but significant in PCa cells to cells a of available prostate and PCa tissue was to the of RIOK1 mRNA expression in PCa of a but significant in RIOK1 mRNA expression in PCa tissue to tissue and was with an to RIOK1 in tissue samples PCa patients radical of the RIOK1 was with RIOK1 cell samples and with an In to the RIOK1 was in the and in the However, in with the a was in PCa tissue the RIOK1 expression was in a tissue and tissue samples PCa patients total of samples were the due to The RIOK1 protein level was significantly elevated in PCa samples to samples However, were RIOK1 and of of the at diagnosis, at diagnosis, 5 stage, to of of in a new of RIOK1 protein expression is by H. H. J. J. R. Li H. of RIOK1 the of and Scopus Google Scholar RIOK1 by N-methyltransferase to by the protein and kinase this it was the expression of the RIOK1 and protein in the expression of all were the cell in the mRNA expression of was significantly elevated in the as well as in PCa cells the the that RIOK1 is in PCa due to a of and the and landscape of a was on tissue samples of PCa and castration-resistant PCa available J. T. A.J. A.J. L. V. Cancer H. clinical to Full Text Full Text PDF PubMed Scopus Google J. G. D. J. I. of clinical in advanced prostate A. 2019; PubMed Scopus Google Scholar and RIOK1 mRNA level was correlated with several proliferative and protein related in RIOK1 expression was correlated with receptor and in cancer and Li S. D. H. M. of RIOK1 and as a prognostic in 2021; PubMed Scopus Google Li T. C. C. expression of RIOK1 is correlated with cancer receptor and cancer 2020; Google Scholar of RIOK1 mRNA expression with and target gene in PCa was of the in and PCa with RIOK1 with RIOK1 The Cancer in a new The Cancer RIOK1 was as a downstream target in a cancer cell C. S. N. T. T. E. of protein with as a novel therapeutic target oncogene for Cancer PubMed Scopus Google Scholar the the of and the of cell-cycle regulators on RIOK1 expression was for and were and the target gene A. C. H. M. P. The gene 1: Full Text Full Text PDF PubMed Scopus Google Scholar RIOK1 mRNA expression was significantly correlated with mRNA expression and of the c-myc/E2F transcription available transcription the I. Lam P. J. Lin C. O. P. E. on the of 2020; PubMed Scopus Google Scholar were to of and transcription in the of RIOK1 in a of cell It was that its protein as well as several transcription to the and of RIOK1 a similar of the RIOK1 protein was and of the were to that is a of RIOK1 RIOK1 protein expression was significantly by nearly with knockdown In RIOK1 knockdown not have effects on protein expression In summary, the that RIOK1 is a downstream target of the cell-cycle c-myc/E2F transcription the the C. I. E. H. E. van der D. A. H. P. M.J. A. F. of in 2021; PubMed Scopus Google Scholar were used to investigate the of cancer cells to RIOK1 RIOK1 was found to be in of cancer cell lines the PCa cell lines and the of RIOK1 RIOK1 and all other in the was significant in RIOK1 and was a strong of RIOK1 with involved in rRNA protein and of transcription was a significant RIOK1 and MYC was found RIOK1 knockdown were cells a to a and a the of RIOK1 were RIOK1 expression was reduced by on mRNA and by at the protein level and the of RIOK1 the of cells was with a significant in the of cells overexpression were by of cells with for RIOK1 and the RIOK1-D324A of RIOK1 on with overexpression of the RIOK1 cell was significantly by nearly In an of the was the that the expression of RIOK1 is for PCa cell that RIOK1 could be a therapeutic target in the treatment of patients with PCa. the therapeutic potential of a of was to the of the of similar to the RIOK1-D324A N. of Rio1 kinase with toyocamycin a that and PubMed Scopus Google F. L. E. J. Zemp I. Kutay U. The kinase of human Rio1 is for final steps of of 40S PubMed Scopus Google Scholar In in and PCa cell PCa cell was with toyocamycin with EC50 values 3.5 to 8.8 and investigate the of in PCa in and cells at a of were and cell related the clinically used chemotherapeutic drug docetaxel was in RIOK1 protein expression was significantly reduced inhibition of RIOK1 that RIOK1 its expression, as in M.G. M. O. L. C. M. V. C. R. D. Ferreira-Cerca S. E. De Wulf P. Rio1 its in PubMed Scopus Google Scholar the of toyocamycin on rRNA was the of RIOK1 in the of rRNA and in the of the M. Zemp I. van den Heuvel J. Thoms M. Berninghausen O. Kutay U. Beckmann R. Structural basis for the final steps of human 40S ribosome maturation.Nature. 2020; 587: 683-687Crossref PubMed Scopus (34) Google S. I. E. N. E. Rio1 kinase/ATPase of pre-40S in PubMed Scopus Google Scholar rRNA per cell was significantly by in cell lines of the rRNA a significant shift in the and with a of rRNA and In RIOK1 protein expression, rRNA per and the rRNA were not significantly with to toyocamycin in PCa the was in and cells cell of toyocamycin and the was to that with docetaxel treatment. the at a of was significantly induced at treatment the of cells with toyocamycin treatment was similar to that with the chemotherapeutic drug that inhibition of RIOK1 with toyocamycin is a of cell in PCa The the that the conserved atypical protein kinase/ATPase RIOK1 is elevated in PCa and for the of PCa The that RIOK1 was at the protein level in PCa cells the of cancer with RIOK1 H. H. J. J. R. Li H. of RIOK1 the of and Scopus Google Scholar, Li S. D. H. M. of RIOK1 and as a prognostic in 2021; PubMed Scopus Google Scholar, R. S. RIOK1 is with cell cancer clinical and to cancer 2022; PubMed Scopus Google F. N. L. S. J. M. S. N. T. N. F. A. S. J. R. T. The atypical kinase RIOK1 and Full Text Full Text PDF PubMed Scopus Google S. L. C. H. J. J. RIOK1 and in cancer of 2022; PubMed Scopus (3) Google Scholar In a by Li T. C. C. expression of RIOK1 is correlated with cancer receptor and cancer 2020; Google Scholar in was and was induced with knockdown of with the in PCa RIOK1 Li T. C. C. expression of RIOK1 is correlated with cancer receptor and cancer 2020; Google Scholar that elevated RIOK1 expression was with and was correlated with receptor Li T. C. C. expression of RIOK1 is correlated with cancer receptor and cancer 2020; Google Scholar In in the study, were found RIOK1 mRNA expression and clinical as stage, of and was found RIOK1 mRNA expression and target gene in PCa. role of RIOK1 in has been in RIOK1 is with Li S. D. H. M. of RIOK1 and as a prognostic in 2021; PubMed Scopus Google Scholar However, in PCa RIOK1 mRNA expression and gene was In RIOK1 was to have cell and a therapeutic of with in patients with RIOK1 expression to that in R. S. RIOK1 is with cell cancer clinical and to cancer 2022; PubMed Scopus Google Scholar of a role of RIOK1 is in RIOK1 was to and to radiation S. L. C. H. J. J. RIOK1 and in cancer of 2022; PubMed Scopus (3) Google Scholar the in RIOK1 protein expression in PCa tissue was is the to at the mRNA This a strong of of the RIOK1 protein level is by to and In RIOK1 was to be on by the and RIOK1 H. H. J. J. R. Li H. of RIOK1 the of and Scopus Google Scholar mRNA expression of all RIOK1 regulators was prostate cell In mRNA expression was significantly elevated in PCa cells and the in In in cancer tissue RIOK1 and protein expression of were to be correlated with RIOK1 protein expression, RIOK1 was correlated with protein expression of H. H. J. J. R. Li H. of RIOK1 the of and Scopus Google Scholar on the the study, it is clear that are to the of RIOK1 in is of interest that has been to a PCa gene with A. L. A. J. J. W.H. D.J. S. R. Van S. J. a prostate cancer gene of its A. PubMed Scopus Google Scholar was to be important for the development of PCa and of D.J. A. A. D. J. J. Nelson C. E. of in prostate cancer is by 2020; 22: PubMed Scopus Google Scholar Thus, it be important to the in be by The several have that RIOK1 in is with the that RIOK1 is a downstream target of the c-myc/E2F cell-cycle MYC is a oncogene in and expression of in PCa has been with reduced and poor P. M. S. M. S. M. M. A. S. landscape of in prostate a to clinical 2022; PubMed Scopus Google Scholar of MYC in castration-resistant PCa has been T. A. N. M. M. F. ribosomal gene expression prostate cancer cells to J 2021; Full Text Full Text PDF PubMed Scopus (5) Google Scholar and of the c-myc/E2F transcription has been in PCa F. S. C. Van den Broeck T. E. Moris L. R. A. I.G. S. G. F. of in prostate cancer 2019; PubMed Scopus Google Scholar RIOK1 has an as a ribosomal in the final steps of pre-40S ribosomal M. Zemp I. van den Heuvel J. Thoms M. Berninghausen O. Kutay U. Beckmann R. Structural basis for the final steps of human 40S ribosome maturation.Nature. 2020; 587: 683-687Crossref PubMed Scopus (34) Google Scholar RIOK1 is an important in the of as a of ribosome J. A. MYC as a of ribosome and protein 10: PubMed Scopus Google Scholar of is a of of the protein D.J. L. J. D. J. A. J. of MYC expression de to inhibition in castration-resistant prostate 2019; PubMed Scopus Google Scholar could investigate as a target has a role in the of androgen in PCa. RIOK1 expression in PCa is by transcription factors, are proliferative regulators in PCa. are known to to prostate by of and protein kinase P. H. Yang L. M. C. D. M. Chen transcription to prostate by and protein kinase 2022; PubMed Scopus Google Scholar are in PCa that is to therapy and M. J. A. C. F. G. J. A. I. I. Van der G. H. The receptor is a for prostate cancer cell and a target for Cancer PubMed Scopus Google Scholar the and the that the c-myc/E2F transcription promote prostate by of The a of RIOK1 and involved in rRNA protein and of RIOK1 an target in the development of therapies for PCa. RIOK1 is of that initiation in PCa is by the eukaryotic initiation is in L. L. O. A. E. N. M. F. N. and is with prostate cancer A. PubMed Scopus Google Scholar to the of RIOK1 in ribosome it is not that RIOK1 inhibition effects in and cell that RIOK1 inhibition have potential in the treatment of patients with PCa. In the therapeutic potential of toyocamycin has been in and in S. L. C. H. J. J. RIOK1 and in cancer of 2022; PubMed Scopus (3) Google Scholar of in cells by toyocamycin was by C.H. and in cells by novel kinase Sci. PubMed Scopus Google Scholar that toyocamycin a and of the The effects of toyocamycin in cells could be to the of and the and in human prostate cancer PubMed Scopus Google Scholar In toyocamycin was not in to inhibition of the by toyocamycin has been with shift and by N. of Rio1 kinase with toyocamycin a that and PubMed Scopus Google Scholar but toyocamycin has been to with other as kinase and protein S. R. A. G. H. Henry R.A. A.J. J. R. inhibition by toyocamycin in cancer 2022; PubMed Scopus Google M. E. D. S. M. T. A. A. J. S. T. H. R. T. M. S. of an for as a of mRNA Cancer J. PubMed Scopus Google Scholar that the effects are due to RIOK1 the effects on and were by overexpression of a RIOK1 of the in the kinase/ATPase the the that toyocamycin led to a in RIOK1 protein and a shift in the 28S/18S In of human RIOK1 and the RIOK1 of rRNA and led to the of F. L. E. J. Zemp I. Kutay U. The kinase of human Rio1 is for final steps of of 40S PubMed Scopus Google E. C. J. M. of to ribosomal in an J. PubMed Scopus Google Scholar overexpression of Rio1 was to lead to a similar of S. I. E. N. E. Rio1 kinase/ATPase of pre-40S in PubMed Scopus Google Scholar The used in this be used for and be to this in PCa that and of the RIOK1 kinase/ATPase have effects on rRNA and However, of potential effects of toyocamycin are It is to that the overexpression of the RIOK1-D324A similar to cell and In the knockdown of RIOK1 effects on and not that the in RIOK1 protein level was it is that RIOK1 remains to However, it is important to that have that Rio1 are on pre-40S other rRNA and to F. L. E. J. Zemp I. Kutay U. The kinase of human Rio1 is for final steps of of 40S PubMed Scopus Google S. I. E. N. E. Rio1 kinase/ATPase of pre-40S in PubMed Scopus Google Scholar inhibition of the RIOK1 kinase/ATPase is to a a in RIOK1 However, are to effects are with the inhibition of the RIOK1 kinase/ATPase with RIOK1 a the drug to to the RIOK1 and to as a potential RIOK1 H. D. P. L. of for therapy 2019; Scopus Google Scholar The efficacy of has been in cancer cell and cell lines were at lead are available for the development of RIOK1 the the that the atypical kinase/ATPase RIOK1 is in PCa tissue and that it is an of several important processes. It is a part of the MYC oncogene and as it could be considered a therapeutic target for future of PCa. for cell for tissue and and for patient The this were in part on by the and and and and and all and and and the with of the samples of PCa and tissue the cell gene expression of the with and RIOK1 and of a PCa cell with RIOK1 expression,

Topics & Concepts