PMID- 35509067
OWN - NLM
STAT- MEDLINE
DCOM- 20220506
LR  - 20220716
IS  - 1479-5876 (Electronic)
IS  - 1479-5876 (Linking)
VI  - 20
IP  - 1
DP  - 2022 May 4
TI  - TPI1 activates the PI3K/AKT/mTOR signaling pathway to induce breast cancer 
      progression by stabilizing CDCA5.
PG  - 191
LID - 10.1186/s12967-022-03370-2 [doi]
LID - 191
AB  - BACKGROUND: Triosephosphate isomerase 1 (TPI1), as a key glycolytic enzyme, is 
      upregulated in multiple cancers. However, expression profile and regulatory 
      mechanism of TPI1 in breast cancer (BRCA) remain mysterious. METHODS: Western 
      blotting and immunohistochemistry (IHC) assays were used to investigate the 
      expression of TPI1 in BRCA specimens and cell lines. TPI1 correlation with the 
      clinicopathological characteristics and prognosis of 362 BRCA patients was 
      analyzed using a tissue microarray. Overexpression and knockdown function 
      experiments in cells and mice models were performed to elucidate the function and 
      mechanisms of TPI1-induced BRCA progression. Related molecular mechanisms were 
      clarified using co-IP, IF, mass spectrometric analysis, and ubiquitination assay. 
      RESULTS: We have found TPI1 is highly expressed in BRCA tissue and cell lines, 
      acting as an independent indicator for prognosis in BRCA patients. TPI1 promotes 
      BRCA cell glycolysis, proliferation and metastasis in vitro and in vivo. 
      Mechanistically, TPI1 activates phosphoinositide 3-kinase (PI3K)/AKT/mammalian 
      target of rapamycin (mTOR) pathway to regulate epithelial-mesenchymal 
      transformation (EMT) and aerobic glycolysis, which is positively mediated by cell 
      division cycle associated 5 (CDCA5). Moreover, TPI1 interacts with sequestosome-1 
      (SQSTM1)/P62, and P62 decreases the protein expression of TPI1 by promoting its 
      ubiquitination in MDA-MB-231 cells. CONCLUSIONS: TPI1 promotes BRCA progression 
      by stabilizing CDCA5, which then activates the PI3K/AKT/mTOR pathway. P62 
      promotes ubiquitin-dependent proteasome degradation of TPI1. Collectively, TPI1 
      promotes tumor development and progression, which may serve as a therapeutic 
      target for BRCA.
CI  - (c) 2022. The Author(s).
FAU - Jin, Xiaoying
AU  - Jin X
AD  - The Fourth Department of Medical Oncology, Harbin Medical University Cancer 
      Hospital, Harbin, 150040, China.
FAU - Wang, Dandan
AU  - Wang D
AD  - The Fourth Department of Medical Oncology, Harbin Medical University Cancer 
      Hospital, Harbin, 150040, China.
FAU - Lei, Mengxia
AU  - Lei M
AD  - The Fourth Department of Medical Oncology, Harbin Medical University Cancer 
      Hospital, Harbin, 150040, China.
FAU - Guo, Yan
AU  - Guo Y
AD  - The Fourth Department of Medical Oncology, Harbin Medical University Cancer 
      Hospital, Harbin, 150040, China.
FAU - Cui, Yuqing
AU  - Cui Y
AD  - The Fourth Department of Medical Oncology, Harbin Medical University Cancer 
      Hospital, Harbin, 150040, China.
FAU - Chen, Fengzhi
AU  - Chen F
AD  - The Fourth Department of Medical Oncology, Harbin Medical University Cancer 
      Hospital, Harbin, 150040, China.
FAU - Sun, Weiling
AU  - Sun W
AD  - Department of Medical Oncology, Harbin Medical University Cancer Hospital, 
      Harbin, 150040, China. sunweiling@hrbmu.edu.cn.
FAU - Chen, Xuesong
AU  - Chen X
AUID- ORCID: 0000-0003-4332-7559
AD  - The Fourth Department of Medical Oncology, Harbin Medical University Cancer 
      Hospital, Harbin, 150040, China. cxs1978@ems.hrbmu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20220504
PL  - England
TA  - J Transl Med
JT  - Journal of translational medicine
JID - 101190741
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (CDCA5 protein, human)
RN  - 0 (Cell Cycle Proteins)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/metabolism
MH  - Animals
MH  - *Breast Neoplasms/genetics
MH  - Cell Cycle Proteins/metabolism
MH  - Cell Line, Tumor
MH  - Cell Movement
MH  - Cell Proliferation
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Mammals/metabolism
MH  - Mice
MH  - Phosphatidylinositol 3-Kinase/metabolism
MH  - *Phosphatidylinositol 3-Kinases/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC9066866
OTO - NOTNLM
OT  - CDCA5
OT  - Epithelial-mesenchymal transformation (EMT)
OT  - Glycolysis
OT  - PI3K/AKT/mTOR
OT  - TPI1
COIS- The authors declare no potential conflicts of interest.
EDAT- 2022/05/06 06:00
MHDA- 2022/05/07 06:00
PMCR- 2022/05/04
CRDT- 2022/05/05 00:09
PHST- 2022/02/09 00:00 [received]
PHST- 2022/03/26 00:00 [accepted]
PHST- 2022/05/05 00:09 [entrez]
PHST- 2022/05/06 06:00 [pubmed]
PHST- 2022/05/07 06:00 [medline]
PHST- 2022/05/04 00:00 [pmc-release]
AID - 10.1186/s12967-022-03370-2 [pii]
AID - 3370 [pii]
AID - 10.1186/s12967-022-03370-2 [doi]
PST - epublish
SO  - J Transl Med. 2022 May 4;20(1):191. doi: 10.1186/s12967-022-03370-2.