PMID- 27491285
OWN - NLM
STAT- MEDLINE
DCOM- 20171025
LR  - 20220330
IS  - 1471-2407 (Electronic)
IS  - 1471-2407 (Linking)
VI  - 16
DP  - 2016 Aug 5
TI  - S6Ks isoforms contribute to viability, migration, docetaxel resistance and tumor 
      formation of prostate cancer cells.
PG  - 602
LID - 10.1186/s12885-016-2629-y [doi]
LID - 602
AB  - BACKGROUND: The S6 Kinase (S6K) proteins are some of the main downstream 
      effectors of the mammalian Target Of Rapamycin (mTOR) and act as key regulators 
      of protein synthesis and cell growth. S6K is overexpressed in a variety of human 
      tumors and is correlated to poor prognosis in prostate cancer. Due to the current 
      urgency to identify factors involved in prostate cancer progression, we aimed to 
      reveal the cellular functions of three S6K isoforms-p70-S6K1, p85-S6K1 and 
      p54-S6K2-in prostate cancer, as well as their potential as therapeutic targets. 
      METHODS: In this study we performed S6K knockdown and overexpression and 
      investigated its role in prostate cancer cell proliferation, colony formation, 
      viability, migration and resistance to docetaxel treatment. In addition, we 
      measured tumor growth in Nude mice injected with PC3 cells overexpressing S6K 
      isoforms and tested the efficacy of a new available S6K1 inhibitor in vitro. 
      RESULTS: S6Ks overexpression enhanced PC3-luc cell line viability, migration, 
      resistance to docetaxel and tumor formation in Nude mice. Only S6K2 knockdown 
      rendered prostate cancer cells more sensitive to docetaxel. S6K1 inhibitor 
      PF-4708671 was particularly effective for reducing migration and proliferation of 
      PC3 cell line. CONCLUSIONS: These findings demonstrate that S6Ks play an 
      important role in prostate cancer progression, enhancing cell viability, 
      migration and chemotherapy resistance, and place both S6K1 and S6K2 as a 
      potential targets in advanced prostate cancer. We also provide evidence that S6K1 
      inhibitor PF-4708671 may be considered as a potential drug for prostate cancer 
      treatment.
FAU - Amaral, Camila L
AU  - Amaral CL
AD  - Laboratory of Disorders of Metabolism, School of Applied Sciences, University of 
      Campinas, R. Pedro Zaccaria, 1300, sala LA 421, 13484-350, Limeira, Sao Paulo, 
      Brazil.
FAU - Freitas, Lidia B
AU  - Freitas LB
AD  - Laboratory of Disorders of Metabolism, School of Applied Sciences, University of 
      Campinas, R. Pedro Zaccaria, 1300, sala LA 421, 13484-350, Limeira, Sao Paulo, 
      Brazil.
FAU - Tamura, Rodrigo E
AU  - Tamura RE
AD  - Viral Vector Laboratory, Center for Translational Investigation in 
      Oncology/LIM24, Cancer Institute of Sao Paulo, School of Medicine, University of 
      Sao Paulo, Sao Paulo, Brazil.
FAU - Tavares, Mariana R
AU  - Tavares MR
AD  - Laboratory of Disorders of Metabolism, School of Applied Sciences, University of 
      Campinas, R. Pedro Zaccaria, 1300, sala LA 421, 13484-350, Limeira, Sao Paulo, 
      Brazil.
FAU - Pavan, Isadora C B
AU  - Pavan IC
AD  - Laboratory of Disorders of Metabolism, School of Applied Sciences, University of 
      Campinas, R. Pedro Zaccaria, 1300, sala LA 421, 13484-350, Limeira, Sao Paulo, 
      Brazil.
FAU - Bajgelman, Marcio C
AU  - Bajgelman MC
AD  - Brazilian Biosciences National Laboratory, Brazilian National Center for Research 
      in Energy and Materials, Campinas, Sao Paulo, Brazil.
FAU - Simabuco, Fernando M
AU  - Simabuco FM
AD  - Laboratory of Disorders of Metabolism, School of Applied Sciences, University of 
      Campinas, R. Pedro Zaccaria, 1300, sala LA 421, 13484-350, Limeira, Sao Paulo, 
      Brazil. simabuco@gmail.com.
LA  - eng
PT  - Journal Article
DEP - 20160805
PL  - England
TA  - BMC Cancer
JT  - BMC cancer
JID - 100967800
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Isoenzymes)
RN  - 0 (Taxoids)
RN  - 15H5577CQD (Docetaxel)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/pharmacology
MH  - Blotting, Western
MH  - Cell Line, Tumor
MH  - Cell Movement/drug effects/physiology
MH  - Cell Survival/drug effects/physiology
MH  - Docetaxel
MH  - Drug Resistance, Neoplasm/physiology
MH  - Enzyme Inhibitors/pharmacology
MH  - Gene Knockdown Techniques
MH  - Heterografts
MH  - Humans
MH  - Isoenzymes/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Nude
MH  - Prostatic Neoplasms/*enzymology/*pathology
MH  - Ribosomal Protein S6 Kinases/*metabolism
MH  - Taxoids/pharmacology
PMC - PMC4974797
OTO - NOTNLM
OT  - Cancer
OT  - S6K
OT  - mTOR
EDAT- 2016/08/06 06:00
MHDA- 2017/10/27 06:00
PMCR- 2016/08/05
CRDT- 2016/08/06 06:00
PHST- 2016/03/24 00:00 [received]
PHST- 2016/07/26 00:00 [accepted]
PHST- 2016/08/06 06:00 [entrez]
PHST- 2016/08/06 06:00 [pubmed]
PHST- 2017/10/27 06:00 [medline]
PHST- 2016/08/05 00:00 [pmc-release]
AID - 10.1186/s12885-016-2629-y [pii]
AID - 2629 [pii]
AID - 10.1186/s12885-016-2629-y [doi]
PST - epublish
SO  - BMC Cancer. 2016 Aug 5;16:602. doi: 10.1186/s12885-016-2629-y.