PMID- 37469018
OWN - NLM
STAT- MEDLINE
DCOM- 20230927
LR  - 20231003
IS  - 2198-3844 (Electronic)
IS  - 2198-3844 (Linking)
VI  - 10
IP  - 27
DP  - 2023 Sep
TI  - PUM1 Promotes Tumor Progression by Activating DEPTOR-Meditated Glycolysis in 
      Gastric Cancer.
PG  - e2301190
LID - 10.1002/advs.202301190 [doi]
LID - 2301190
AB  - RNA-binding proteins (RBPs) play essential roles in tumorigenesis and 
      progression, but their functions in gastric cancer (GC) remain largely elusive. 
      Here, it is reported that Pumilio 1 (PUM1), an RBP, induces metabolic 
      reprogramming through post-transcriptional regulation of DEP domain-containing 
      mammalian target of rapamycin (mTOR)-interacting protein (DEPTOR) in GC. In 
      clinical samples, elevated expression of PUM1 is associated with recurrence, 
      metastasis, and poor survival. In vitro and in vivo experiments demonstrate that 
      knockdown of PUM1 inhibits the proliferation and metastasis of GC cells. In 
      addition, RNA-sequencing and bioinformatics analyses show that PUM1 is enriched 
      in the glycolysis gene signature. Metabolomics studies confirm that PUM1 
      deficiency suppresses glycolytic metabolism. Mechanistically, PUM1 binds directly 
      to DEPTOR mRNA pumilio response element to maintain the stability of the 
      transcript and prevent DEPTOR degradation through post-transcriptional pathway. 
      PUM1-mediated DEPTOR upregulation inhibits mTORC1 and alleviates the inhibitory 
      feedback signal transmitted from mTORC1 to PI3K under normal conditions, thus 
      activating the PI3K-Akt signal and glycolysis continuously. Collectively, these 
      results reveal the critical epigenetic role of PUM1 in modulating 
      DEPTOR-dependent GC progression. These conclusions support further clinical 
      investigation of PUM1 inhibitors as a metabolic-targeting treatment strategy for 
      GC.
CI  - (c) 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.
FAU - Yin, Songcheng
AU  - Yin S
AD  - Digestive Diseases Center, Guangdong Provincial Key Laboratory of Digestive 
      Cancer Research, The Seventh Affiliated Hospital of Sun Yat-sen University, 
      Shenzhen, Guangdong, 518107, China.
FAU - Liu, Huifang
AU  - Liu H
AD  - Digestive Diseases Center, Guangdong Provincial Key Laboratory of Digestive 
      Cancer Research, The Seventh Affiliated Hospital of Sun Yat-sen University, 
      Shenzhen, Guangdong, 518107, China.
AD  - Department of Radiotherapy, Affiliated Cancer Hospital of Zhengzhou University, 
      Henan Cancer Hospital, Zhengzhou, Henan, 450000, China.
FAU - Zhou, Zhijun
AU  - Zhou Z
AD  - Department of Medicine, The University of Oklahoma Health Sciences Center, 
      Oklahoma City, OK 73104, USA.
FAU - Xu, Xiaoyu
AU  - Xu X
AD  - Department of Gynecology and Obstetrics, The Seventh Affiliated Hospital of Sun 
      Yat-sen University, Shenzhen, Guangdong, 518107, China.
FAU - Wang, Pengliang
AU  - Wang P
AD  - Department of Gastrointestinal Surgery, Sun Yat-sen Memorial Hospital, Sun 
      Yat-sen University, Guangzhou, Guangdong, 510120, China.
FAU - Chen, Wei
AU  - Chen W
AD  - Digestive Diseases Center, Guangdong Provincial Key Laboratory of Digestive 
      Cancer Research, The Seventh Affiliated Hospital of Sun Yat-sen University, 
      Shenzhen, Guangdong, 518107, China.
FAU - Deng, Guofei
AU  - Deng G
AD  - Digestive Diseases Center, Guangdong Provincial Key Laboratory of Digestive 
      Cancer Research, The Seventh Affiliated Hospital of Sun Yat-sen University, 
      Shenzhen, Guangdong, 518107, China.
FAU - Wang, Han
AU  - Wang H
AD  - Digestive Diseases Center, Guangdong Provincial Key Laboratory of Digestive 
      Cancer Research, The Seventh Affiliated Hospital of Sun Yat-sen University, 
      Shenzhen, Guangdong, 518107, China.
FAU - Yu, Hong
AU  - Yu H
AD  - Digestive Diseases Center, Guangdong Provincial Key Laboratory of Digestive 
      Cancer Research, The Seventh Affiliated Hospital of Sun Yat-sen University, 
      Shenzhen, Guangdong, 518107, China.
FAU - Gu, Liang
AU  - Gu L
AD  - Digestive Diseases Center, Guangdong Provincial Key Laboratory of Digestive 
      Cancer Research, The Seventh Affiliated Hospital of Sun Yat-sen University, 
      Shenzhen, Guangdong, 518107, China.
FAU - Huo, Mingyu
AU  - Huo M
AD  - Digestive Diseases Center, Guangdong Provincial Key Laboratory of Digestive 
      Cancer Research, The Seventh Affiliated Hospital of Sun Yat-sen University, 
      Shenzhen, Guangdong, 518107, China.
FAU - Li, Min
AU  - Li M
AD  - Department of Medicine, The University of Oklahoma Health Sciences Center, 
      Oklahoma City, OK 73104, USA.
FAU - Zeng, Leli
AU  - Zeng L
AD  - Digestive Diseases Center, Guangdong Provincial Key Laboratory of Digestive 
      Cancer Research, The Seventh Affiliated Hospital of Sun Yat-sen University, 
      Shenzhen, Guangdong, 518107, China.
FAU - He, Yulong
AU  - He Y
AD  - Digestive Diseases Center, Guangdong Provincial Key Laboratory of Digestive 
      Cancer Research, The Seventh Affiliated Hospital of Sun Yat-sen University, 
      Shenzhen, Guangdong, 518107, China.
AD  - Department of Gastrointestinal Surgery, The First Affiliated Hospital of Sun 
      Yat-sen University, Guangzhou, Guangdong, 510062, China.
FAU - Zhang, Changhua
AU  - Zhang C
AUID- ORCID: 0000-0003-4358-4096
AD  - Digestive Diseases Center, Guangdong Provincial Key Laboratory of Digestive 
      Cancer Research, The Seventh Affiliated Hospital of Sun Yat-sen University, 
      Shenzhen, Guangdong, 518107, China.
LA  - eng
GR  - 82003104/National Natural Science Foundation of China/
GR  - 82073148/National Natural Science Foundation of China/
GR  - 81772579/National Natural Science Foundation of China/
GR  - 2021B1212040006/Guangdong Provincial Key Laboratory of Digestive Cancer Research/
GR  - 2019A1515110632/Guangdong Basic and Applied Basic Research Foundation/
GR  - SZSM201612022/Sanming Project of Medicine in Shenzhen/
GR  - KCXFZ202002011010593/Shenzhen Sustainable Project/
GR  - 2021T140768/China Postdoctoral Science Foundation/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230719
PL  - Germany
TA  - Adv Sci (Weinh)
JT  - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
JID - 101664569
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - 0 (PUM1 protein, human)
RN  - 0 (RNA-Binding Proteins)
RN  - EC 2.7.1.1 (DEPTOR protein, human)
SB  - IM
MH  - Humans
MH  - *Signal Transduction
MH  - Phosphatidylinositol 3-Kinases
MH  - Intracellular Signaling Peptides and Proteins/metabolism
MH  - *Stomach Neoplasms/genetics
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Mechanistic Target of Rapamycin Complex 1/metabolism
MH  - RNA-Binding Proteins/genetics/metabolism
PMC - PMC10520643
OTO - NOTNLM
OT  - DEPTOR
OT  - PI3K-Akt pathway
OT  - PUM1
OT  - gastric cancer
OT  - glycolysis
COIS- The authors declare no conflict of interest. All these study sponsors have no 
      roles in the study design, in the collection, analysis and interpretation of 
      data.
EDAT- 2023/07/20 06:42
MHDA- 2023/09/27 06:42
PMCR- 2023/07/19
CRDT- 2023/07/20 00:03
PHST- 2023/07/05 00:00 [revised]
PHST- 2023/02/21 00:00 [received]
PHST- 2023/09/27 06:42 [medline]
PHST- 2023/07/20 06:42 [pubmed]
PHST- 2023/07/20 00:03 [entrez]
PHST- 2023/07/19 00:00 [pmc-release]
AID - ADVS6176 [pii]
AID - 10.1002/advs.202301190 [doi]
PST - ppublish
SO  - Adv Sci (Weinh). 2023 Sep;10(27):e2301190. doi: 10.1002/advs.202301190. Epub 2023 
      Jul 19.