PMID- 30338032
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 9
IP  - 74
DP  - 2018 Sep 21
TI  - IRS-2 deubiquitination by USP9X maintains anchorage-independent cell growth via 
      Erk1/2 activation in prostate carcinoma cell line.
PG  - 33871-33883
LID - 10.18632/oncotarget.26049 [doi]
AB  - Insulin-like growth factors (IGFs) have been shown to induce proliferation of 
      many types of cells. Insulin receptor substrates (IRSs) are major targets of 
      IGF-I receptor (IGF-IR) tyrosine kinase activated by IGFs, and are known to play 
      important roles in the activation of downstream signaling pathways, such as the 
      Erk1/2 pathway. Dysregulation of IGF signaling represents a central tumor 
      promoting principle in human carcinogenesis. Prostate carcinoma is highly 
      dependent on the IGF/IGF-IR/IRS axis. Here we identified the deubiquitinase, 
      ubiquitin specific peptidase 9X (USP9X) as a novel binding partner of IRS-2. In a 
      human prostate carcinoma cell line, small interfering RNA (siRNA)-mediated 
      knockdown of USP9X reduced IGF-IR as well as IRS-2 protein levels and increased 
      their ubiquitination. Knockdown of USP9X suppressed basal activation of the 
      Erk1/2 pathway, which was significantly restored by exogenous expression of IRS-2 
      but not by IGF-IR, suggesting that the stabilization of IRS-2 by USP9X is 
      critical for basal Erk1/2 activation. Finally, we measured anchorage-independent 
      cell growth, a characteristic cancer feature, by soft-agar colony formation 
      assay. Knockdown of USP9X significantly reduced anchorage-independent cell growth 
      of prostate carcinoma cell line. Taken all together, our findings indicate that 
      USP9X is required for the promotion of prostate cancer growth by maintaining the 
      activation of the Erk1/2 pathway through IRS-2 stabilization.
FAU - Furuta, Haruka
AU  - Furuta H
AD  - Departments of Animal Sciences and Applied Biological Chemistry, Graduate School 
      of Agriculture and Life Sciences, The University of Tokyo, Tokyo, Japan.
FAU - Yoshihara, Hidehito
AU  - Yoshihara H
AD  - Departments of Animal Sciences and Applied Biological Chemistry, Graduate School 
      of Agriculture and Life Sciences, The University of Tokyo, Tokyo, Japan.
FAU - Fukushima, Toshiaki
AU  - Fukushima T
AD  - Department of Medical Science, Graduate School of Medicine, Hiroshima University, 
      Hiroshima, Japan.
AD  - Cell Biology Center, Institute of Innovative Research, Tokyo Institute of 
      Technology, Yokohama, Japan.
FAU - Yoneyama, Yosuke
AU  - Yoneyama Y
AD  - Departments of Animal Sciences and Applied Biological Chemistry, Graduate School 
      of Agriculture and Life Sciences, The University of Tokyo, Tokyo, Japan.
AD  - Present address: Institute of Research, Tokyo Medical and Dental University, 
      Tokyo, Japan.
FAU - Ito, Akihiro
AU  - Ito A
AD  - Chemical Genomics Research Group, RIKEN Center for Sustainable Resource Science, 
      Saitama, Japan.
FAU - Worrall, Claire
AU  - Worrall C
AD  - Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska 
      Institute and Karolinska University Hospital, Stockholm, Sweden.
FAU - Girnita, Ada
AU  - Girnita A
AD  - Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska 
      Institute and Karolinska University Hospital, Stockholm, Sweden.
FAU - Girnita, Leonard
AU  - Girnita L
AD  - Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska 
      Institute and Karolinska University Hospital, Stockholm, Sweden.
FAU - Yoshida, Minoru
AU  - Yoshida M
AD  - Chemical Genomics Research Group, RIKEN Center for Sustainable Resource Science, 
      Saitama, Japan.
FAU - Asano, Tomoichiro
AU  - Asano T
AD  - Department of Medical Science, Graduate School of Medicine, Hiroshima University, 
      Hiroshima, Japan.
FAU - Komada, Masayuki
AU  - Komada M
AD  - Cell Biology Center, Institute of Innovative Research, Tokyo Institute of 
      Technology, Yokohama, Japan.
FAU - Kataoka, Naoyuki
AU  - Kataoka N
AD  - Departments of Animal Sciences and Applied Biological Chemistry, Graduate School 
      of Agriculture and Life Sciences, The University of Tokyo, Tokyo, Japan.
FAU - Chida, Kazuhiro
AU  - Chida K
AD  - Departments of Animal Sciences and Applied Biological Chemistry, Graduate School 
      of Agriculture and Life Sciences, The University of Tokyo, Tokyo, Japan.
FAU - Hakuno, Fumihiko
AU  - Hakuno F
AD  - Departments of Animal Sciences and Applied Biological Chemistry, Graduate School 
      of Agriculture and Life Sciences, The University of Tokyo, Tokyo, Japan.
FAU - Takahashi, Shin-Ichiro
AU  - Takahashi SI
AD  - Departments of Animal Sciences and Applied Biological Chemistry, Graduate School 
      of Agriculture and Life Sciences, The University of Tokyo, Tokyo, Japan.
LA  - eng
PT  - Journal Article
DEP - 20180921
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
PMC - PMC6188063
OTO - NOTNLM
OT  - IGF-I
OT  - IRS-2
OT  - USP9X
OT  - prostate cancer
OT  - ubiquitin
COIS- CONFLICTS OF INTEREST The authors declare no conflicts of interest associated 
      with this manuscript.
EDAT- 2018/10/20 06:00
MHDA- 2018/10/20 06:01
PMCR- 2018/09/21
CRDT- 2018/10/20 06:00
PHST- 2018/03/07 00:00 [received]
PHST- 2018/07/21 00:00 [accepted]
PHST- 2018/10/20 06:00 [entrez]
PHST- 2018/10/20 06:00 [pubmed]
PHST- 2018/10/20 06:01 [medline]
PHST- 2018/09/21 00:00 [pmc-release]
AID - 26049 [pii]
AID - 10.18632/oncotarget.26049 [doi]
PST - epublish
SO  - Oncotarget. 2018 Sep 21;9(74):33871-33883. doi: 10.18632/oncotarget.26049. 
      eCollection 2018 Sep 21.