PMID- 36601406
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230111
IS  - 1664-302X (Print)
IS  - 1664-302X (Electronic)
IS  - 1664-302X (Linking)
VI  - 13
DP  - 2022
TI  - Streptococcus pneumoniae promotes migration and invasion of A549 cells in vitro 
      by activating mTORC2/AKT through up-regulation of DDIT4 expression.
PG  - 1046226
LID - 10.3389/fmicb.2022.1046226 [doi]
LID - 1046226
AB  - INTRODUCTION: Dysbiosis of the lower airway flora is associated with lung cancer, 
      of which the relationship between Streptococcus, especially pathogenic 
      Streptococcus pneumoniae (S. pneumoniae), and the progression of lung cancer are 
      unclear. METHODS: Bronchoalveolar lavage fluid (BALF) samples were prospectively 
      collected from patients with pulmonary nodules during diagnostic bronchoscopy, 
      and finally included 70 patients diagnosed with primary lung cancer and 20 
      patients with benign pulmonary nodules as the disease control group. The 
      differential flora was screened by 16S ribosomal RNA (rRNA) gene amplicon 
      sequencing. An in vitro infection model of lung adenocarcinoma (LUAD) cells 
      exposed to S.pneumoniae was established to observe its effects on cell migration 
      and invasion ability. Exploring the molecular mechanisms downstream of DDIT4 
      through its loss- and gain-of-function experiments. RESULTS: 16S rRNA sequencing 
      analysis showed that the abundance of Streptococcus in the lower airway flora of 
      lung cancer patients was significantly increased. After exposure to S. 
      pneumoniae, A549 and H1299 cells significantly enhanced their cell migration and 
      invasion ability. The results of DDIT4 loss- and gain-of-function experiments in 
      A549 cells suggest that up-regulation of DDIT4 activates the mTORC2/Akt signaling 
      pathway, thereby enhancing the migration and invasion of A549 cells while not 
      affecting mTORC1. Immunofluorescence (IF) and fluorescence in situ hybridization 
      (FISH) showed that S. pneumoniae was enriched in LUAD tissues, and DDIT4 
      expression was significantly higher in cancer tissues than in non-cancerous 
      tissues. The increased expression of DDIT4 was also related to the poor prognosis 
      of patients with LUAD. DISCUSSION: The data provided by this study show that S. 
      pneumoniae enriched in the lower airway of patients with lung cancer can 
      up-regulate DDIT4 expression and subsequently activate the mTORC2/AKT signal 
      pathway, thereby increasing the migration and invasion abilities of A549 cells. 
      Our study provides a potential new mechanism for targeted therapy of LUAD.
CI  - Copyright (c) 2022 Song, Liu, Zhao, Pu, Liu, Ding and Xue.
FAU - Song, Xiaojie
AU  - Song X
AD  - Department of Pulmonary and Critical Care Medicine, Qilu Hospital of Shandong 
      University, Qingdao, China.
FAU - Liu, Baohong
AU  - Liu B
AD  - Department of Hospital Infection Management, Qilu Hospital of Shandong 
      University, Qingdao, China.
FAU - Zhao, Guanghui
AU  - Zhao G
AD  - Medical Laboratory Center and Oncology Laboratory, Qilu Hospital of Shandong 
      University, Qingdao, China.
FAU - Pu, Xiaoxin
AU  - Pu X
AD  - Department of Pulmonary and Critical Care Medicine, Qilu Hospital of Shandong 
      University, Qingdao, China.
FAU - Liu, Baoyi
AU  - Liu B
AD  - Department of Pulmonary and Critical Care Medicine, Qilu Hospital of Shandong 
      University, Qingdao, China.
FAU - Ding, Meiling
AU  - Ding M
AD  - Department of Infectious Diseases, Qilu Hospital of Shandong University, Qingdao, 
      China.
FAU - Xue, Yuwen
AU  - Xue Y
AD  - Department of Pulmonary and Critical Care Medicine, Qilu Hospital of Shandong 
      University, Jinan, China.
LA  - eng
PT  - Journal Article
DEP - 20221219
PL  - Switzerland
TA  - Front Microbiol
JT  - Frontiers in microbiology
JID - 101548977
PMC - PMC9806147
OTO - NOTNLM
OT  - AKT
OT  - DDIT4
OT  - lung cancer
OT  - mTORC1/2
OT  - migration and invasion
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/01/06 06:00
MHDA- 2023/01/06 06:01
PMCR- 2022/12/19
CRDT- 2023/01/05 02:31
PHST- 2022/09/26 00:00 [received]
PHST- 2022/11/25 00:00 [accepted]
PHST- 2023/01/05 02:31 [entrez]
PHST- 2023/01/06 06:00 [pubmed]
PHST- 2023/01/06 06:01 [medline]
PHST- 2022/12/19 00:00 [pmc-release]
AID - 10.3389/fmicb.2022.1046226 [doi]
PST - epublish
SO  - Front Microbiol. 2022 Dec 19;13:1046226. doi: 10.3389/fmicb.2022.1046226. 
      eCollection 2022.