PMID- 38218360
OWN - NLM
STAT- MEDLINE
DCOM- 20240204
LR  - 20240223
IS  - 1096-0384 (Electronic)
IS  - 0003-9861 (Linking)
VI  - 752
DP  - 2024 Feb
TI  - FKBP38 suppresses endometrial cancer cell proliferation and metastasis by 
      inhibiting the mTOR pathway.
PG  - 109891
LID - S0003-9861(24)00010-9 [pii]
LID - 10.1016/j.abb.2024.109891 [doi]
AB  - Endometrial cancer (EC) is a common gynecological malignancy, and advanced-stage 
      or recurrent EC is associated with a high mortality rate owing to the 
      ineffectiveness of currently available treatments. FK506-binding protein 38 
      (FKBP38) is a member of the immunophilin family and inhibits melanoma and breast 
      cancer cell metastasis. However, the functions of FKBP38 and its potential 
      mechanism in EC remain unclear. Herein, we analyzed the expression levels of 
      FKBP38 in EC cells and found that the FKBP38 expression was high in Ishikawa 
      cells, and low in AN3CA cells, traditionally considered a low grade and a high 
      grade cell line, respectively, in pathology classification. Moreover, FKBP38 
      inhibited cell proliferation, migration and invasion in EC cells, FKBP38 
      knockdown significantly promoted tumor growth of Ishikawa cells in a subcutaneous 
      xenograft model and increased the number of lung metastases of Hec-1-A cells in a 
      metastatic mouse model. Furthermore, FKBP38 suppressed several target proteins of 
      epithelial-to-mesenchymal transition (EMT) and reduced the phosphorylation of 
      ribosomal S6 protein (S6), eukaryotic initiation factor 4E-binding protein 1 
      (4EBP-1), indicating the potent inhibition of the mammalian target of rapamycin 
      (mTOR) pathway. Meanwhile, the inhibition of mTOR neutralized the elevation of EC 
      cell proliferation, migration and invasion after FKBP38 knockdown. In summary, 
      FKBP38 would exert a tumor-suppressing role by modulating the mTOR pathway. Our 
      results indicate that FKBP38 may be considered as a factor of EC metastasis and a 
      new target for EC therapeutic intervention.
CI  - Copyright (c) 2024 Elsevier Inc. All rights reserved.
FAU - Yan, Yunjing
AU  - Yan Y
AD  - The School of Biomedical and Pharmaceutical Sciences, Guangdong University of 
      Technology, Guangzhou, Guangdong Province, PR China.
FAU - Wang, Shuai
AU  - Wang S
AD  - The School of Biomedical and Pharmaceutical Sciences, Guangdong University of 
      Technology, Guangzhou, Guangdong Province, PR China.
FAU - Zhang, Zongmeng
AU  - Zhang Z
AD  - The School of Biomedical and Pharmaceutical Sciences, Guangdong University of 
      Technology, Guangzhou, Guangdong Province, PR China.
FAU - Tang, Minyi
AU  - Tang M
AD  - The School of Biomedical and Pharmaceutical Sciences, Guangdong University of 
      Technology, Guangzhou, Guangdong Province, PR China.
FAU - Zhao, Allan Z
AU  - Zhao AZ
AD  - The School of Biomedical and Pharmaceutical Sciences, Guangdong University of 
      Technology, Guangzhou, Guangdong Province, PR China.
FAU - Li, Zhuang
AU  - Li Z
AD  - The School of Biomedical and Pharmaceutical Sciences, Guangdong University of 
      Technology, Guangzhou, Guangdong Province, PR China.
FAU - Wu, Xiaoli
AU  - Wu X
AD  - The School of Biomedical and Pharmaceutical Sciences, Guangdong University of 
      Technology, Guangzhou, Guangdong Province, PR China. Electronic address: 
      wuxiaoli@gdut.edu.cn.
FAU - Li, Fanghong
AU  - Li F
AD  - The School of Biomedical and Pharmaceutical Sciences, Guangdong University of 
      Technology, Guangzhou, Guangdong Province, PR China. Electronic address: 
      fli@gdut.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20240111
PL  - United States
TA  - Arch Biochem Biophys
JT  - Archives of biochemistry and biophysics
JID - 0372430
RN  - EC 5.2.1.- (Tacrolimus Binding Proteins)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - 0 (FKBP8 protein, human)
RN  - EC 2.7.1.1 (MTOR protein, human)
SB  - IM
MH  - Animals
MH  - Female
MH  - Humans
MH  - Mice
MH  - Cell Line, Tumor
MH  - Cell Movement
MH  - Cell Proliferation
MH  - *Endometrial Neoplasms/metabolism
MH  - Mammals/metabolism
MH  - Signal Transduction/physiology
MH  - *Tacrolimus Binding Proteins/metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
OTO - NOTNLM
OT  - EMT pathway
OT  - Endometrial cancer
OT  - FKBP38
OT  - Metastasis
OT  - Proliferation
OT  - mTOR pathway
COIS- Declaration of competing interest The authors declare no potential conflicts of 
      interest.
EDAT- 2024/01/14 12:42
MHDA- 2024/01/29 06:43
CRDT- 2024/01/13 19:31
PHST- 2023/08/20 00:00 [received]
PHST- 2023/12/26 00:00 [revised]
PHST- 2024/01/10 00:00 [accepted]
PHST- 2024/01/29 06:43 [medline]
PHST- 2024/01/14 12:42 [pubmed]
PHST- 2024/01/13 19:31 [entrez]
AID - S0003-9861(24)00010-9 [pii]
AID - 10.1016/j.abb.2024.109891 [doi]
PST - ppublish
SO  - Arch Biochem Biophys. 2024 Feb;752:109891. doi: 10.1016/j.abb.2024.109891. Epub 
      2024 Jan 11.