PMID- 37879960
OWN - NLM
STAT- MEDLINE
DCOM- 20231216
LR  - 20240206
IS  - 2211-5463 (Electronic)
IS  - 2211-5463 (Linking)
VI  - 13
IP  - 12
DP  - 2023 Dec
TI  - Death receptor 5 promotes tumor progression in gastric cancer.
PG  - 2375-2388
LID - 10.1002/2211-5463.13725 [doi]
AB  - Death receptor 5 (DR5) can inhibit malignant proliferation via tumor necrosis 
      factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in many 
      cancers. Here we examined the expression and sublocalization of DR5 in gastric 
      cancer, as well as its effects on clinical prognosis and cellular processes. Our 
      analysis included a cohort of 240 gastric cancer patients. Bioinformatic analysis 
      showed a significant correlation between DR5 and DNA replication, tumor mutation 
      burden (TMB), and tumor stemness. Unlike death receptor 4 (DR4TRAIL-R1), DR5 was 
      expressed in the cytoplasm and nucleus, and was found to be positively correlated 
      with lymphovascular invasion, lymph node metastasis, and TNM stage. Patients with 
      positive DR5 had worse overall survival (OS) (P = 0.006). The multivariate Cox 
      model showed that DR5 is an independent poor prognostic factor (hazard 
      ratio = 1.693). Furthermore, knockdown of DR5 inhibited aggressive behaviors, 
      including proliferation and metastasis in gastric cancer cells, and inhibited 
      lung metastasis in vivo. In summary, nuclear localization of DR5 expression is a 
      poor prognosis factor in gastric cancer and promotes growth, invasion, and 
      metastasis of tumor cells in vitro and in vivo.
CI  - (c) 2023 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of 
      Federation of European Biochemical Societies.
FAU - Chen, Junbing
AU  - Chen J
AUID- ORCID: 0000-0002-5741-1332
AD  - Department of Gastrointestinal Cancer Translational Research, Key Laboratory of 
      Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking 
      University Cancer Hospital & Institute, Beijing, China.
FAU - Li, Lin
AU  - Li L
AD  - Department of Gastrointestinal Cancer Translational Research, Key Laboratory of 
      Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking 
      University Cancer Hospital & Institute, Beijing, China.
AD  - Department of Gastroenterology, Aerospace Center Hospital, Peking University 
      Aerospace School of Clinical Medicine, Beijing, China.
FAU - Huangfu, Longtao
AU  - Huangfu L
AD  - Department of Gastrointestinal Cancer Translational Research, Key Laboratory of 
      Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking 
      University Cancer Hospital & Institute, Beijing, China.
FAU - Du, Hong
AU  - Du H
AD  - Department of Gastrointestinal Cancer Translational Research, Key Laboratory of 
      Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking 
      University Cancer Hospital & Institute, Beijing, China.
FAU - Ji, Xin
AU  - Ji X
AD  - Gastrointestinal Cancer Center, Key Laboratory of Carcinogenesis and 
      Translational Research (Ministry of Education/Beijing), Peking University Cancer 
      Hospital and Institute, Beijing, China.
FAU - Xing, Xiaofang
AU  - Xing X
AD  - Department of Gastrointestinal Cancer Translational Research, Key Laboratory of 
      Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking 
      University Cancer Hospital & Institute, Beijing, China.
FAU - Ji, Jiafu
AU  - Ji J
AD  - Department of Gastrointestinal Cancer Translational Research, Key Laboratory of 
      Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking 
      University Cancer Hospital & Institute, Beijing, China.
AD  - Gastrointestinal Cancer Center, Key Laboratory of Carcinogenesis and 
      Translational Research (Ministry of Education/Beijing), Peking University Cancer 
      Hospital and Institute, Beijing, China.
LA  - eng
GR  - PX2019039/Beijing Municipal Administration of Hospitals/
GR  - 81872502/National Natural Science Foundation of China/
GR  - 81902985/National Natural Science Foundation of China/
GR  - 82203579/National Natural Science Foundation of China/
GR  - JC202304/Science Foundation of Peking University Cancer Hospital/
GR  - 7222023/Natural Science Foundation of Beijing/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20231114
PL  - England
TA  - FEBS Open Bio
JT  - FEBS open bio
JID - 101580716
RN  - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (TNFRSF10B protein, human)
SB  - IM
MH  - Humans
MH  - Apoptosis/genetics
MH  - *Lung Neoplasms/metabolism
MH  - Neoplastic Processes
MH  - Receptors, TNF-Related Apoptosis-Inducing Ligand/genetics/metabolism
MH  - *Stomach Neoplasms/genetics/pathology
PMC - PMC10699099
OTO - NOTNLM
OT  - TRAIL receptors
OT  - apoptosis
OT  - death receptor 5
OT  - gastric cancer
OT  - nuclear localization
COIS- The authors declare no conflicts of interest. The funders had no role in the 
      design of the study; in the collection, analyses, or interpretation of data; in 
      the writing of the article; or in the decision to publish the results.
EDAT- 2023/10/26 00:42
MHDA- 2023/12/07 12:42
PMCR- 2023/11/14
CRDT- 2023/10/25 21:53
PHST- 2023/09/07 00:00 [revised]
PHST- 2023/02/25 00:00 [received]
PHST- 2023/10/13 00:00 [accepted]
PHST- 2023/12/07 12:42 [medline]
PHST- 2023/10/26 00:42 [pubmed]
PHST- 2023/10/25 21:53 [entrez]
PHST- 2023/11/14 00:00 [pmc-release]
AID - FEB413725 [pii]
AID - 10.1002/2211-5463.13725 [doi]
PST - ppublish
SO  - FEBS Open Bio. 2023 Dec;13(12):2375-2388. doi: 10.1002/2211-5463.13725. Epub 2023 
      Nov 14.