PMID- 32332698
OWN - NLM
STAT- MEDLINE
DCOM- 20210331
LR  - 20211204
IS  - 2041-4889 (Electronic)
VI  - 11
IP  - 4
DP  - 2020 Apr 24
TI  - FADS1 promotes the progression of laryngeal squamous cell carcinoma through 
      activating AKT/mTOR signaling.
PG  - 272
LID - 10.1038/s41419-020-2457-5 [doi]
LID - 272
AB  - Metabolic abnormality is the major feature of laryngeal squamous cell carcinoma 
      (LSCC), however, the underlying mechanism remain largely elusive. Fatty acid 
      desaturase 1 (FADS1), as the key rate-limiting enzyme of polyunsaturated fatty 
      acids (PUFAs), catalyzes dihomo-gamma-linolenic acid (DGLA) to arachidonic acid 
      (AA). In this study, we reported that the expression of FADS1 was upregulated in 
      LSCC, high FADS1 expression was closely associated with the advanced clinical 
      features and poor prognosis of the recurrent LSCC patients after chemotherapy. 
      Liquid chromatograph-mass spectrometry (LC-MS) analysis revealed that FADS1 
      overexpression induced greater conversion of DGLA to AA, suggesting an increased 
      activity of FADS1. Similarly, the level of prostaglandin E2 (PGE(2)), a 
      downstream metabolite of AA, was also elevated in cancerous laryngeal tissues. 
      Functional assays showed that FADS1 knockdown suppressed the proliferation, 
      migration and invasion of LSCC cells, while FADS1 overexpression had the opposite 
      effects. Bioinformatic analysis based on microarray data found that FADS1 could 
      activate AKT/mTOR signaling. This hypothesis was further validated by both in 
      vivo and in vitro assays. Hence, our data has supported the viewpoint that FADS1 
      is a potential promoter in LSCC progression, and has laid the foundation for 
      further functional research on the PUFA dietary supplementation interventions 
      targeting FADS1/AKT/mTOR pathway for LSCC prevention and treatment.
FAU - Zhao, Rui
AU  - Zhao R
AD  - Department of Otolaryngology-Head and Neck Surgery, the Second Affiliated 
      Hospital of Harbin Medical University, Harbin, China.
FAU - Tian, Linli
AU  - Tian L
AD  - Department of Otolaryngology-Head and Neck Surgery, the Second Affiliated 
      Hospital of Harbin Medical University, Harbin, China.
FAU - Zhao, Bo
AU  - Zhao B
AD  - College of Life Science, Northeast Forestry University, Harbin, China.
FAU - Sun, Yanan
AU  - Sun Y
AD  - Department of Otolaryngology-Head and Neck Surgery, the Second Affiliated 
      Hospital of Harbin Medical University, Harbin, China.
FAU - Cao, Jing
AU  - Cao J
AD  - Department of Otolaryngology-Head and Neck Surgery, the Second Affiliated 
      Hospital of Harbin Medical University, Harbin, China.
FAU - Chen, Kexin
AU  - Chen K
AD  - Department of Pathology, the Third Affiliated Hospital of Harbin Medical 
      University, Harbin, China.
FAU - Li, Fengqing
AU  - Li F
AD  - Department of Gerontology, the Second Affiliated Hospital of Harbin Medical 
      University, Harbin, China.
FAU - Li, Minghua
AU  - Li M
AD  - Department of Otolaryngology-Head and Neck Surgery, the Second Affiliated 
      Hospital of Harbin Medical University, Harbin, China.
FAU - Shang, Desi
AU  - Shang D
AD  - College of Bioinformatics Science and Technology, Harbin Medical University, 
      Harbin, China. sds_46@163.com.
FAU - Liu, Ming
AU  - Liu M
AUID- ORCID: 0000-0002-5957-0142
AD  - Department of Otolaryngology-Head and Neck Surgery, the Second Affiliated 
      Hospital of Harbin Medical University, Harbin, China. liumingent@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200424
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (Delta-5 Fatty Acid Desaturase)
RN  - EC 1.14.19.- (Fatty Acid Desaturases)
RN  - EC 1.14.19.3 (FADS1 protein, human)
RN  - EC 1.14.19.3 (FADS1 protein, mouse)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Carcinoma, Squamous Cell/*physiopathology
MH  - Delta-5 Fatty Acid Desaturase
MH  - Disease Progression
MH  - Fatty Acid Desaturases/*adverse effects/metabolism
MH  - Humans
MH  - Laryngeal Neoplasms/*physiopathology
MH  - Male
MH  - Mice
MH  - Mice, Nude
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/*adverse effects/metabolism
MH  - Transfection
PMC - PMC7181692
COIS- The authors declare that they have no conflict of interest.
EDAT- 2020/04/26 06:00
MHDA- 2021/04/01 06:00
PMCR- 2020/04/24
CRDT- 2020/04/26 06:00
PHST- 2019/08/17 00:00 [received]
PHST- 2020/04/07 00:00 [accepted]
PHST- 2020/04/07 00:00 [revised]
PHST- 2020/04/26 06:00 [entrez]
PHST- 2020/04/26 06:00 [pubmed]
PHST- 2021/04/01 06:00 [medline]
PHST- 2020/04/24 00:00 [pmc-release]
AID - 10.1038/s41419-020-2457-5 [pii]
AID - 2457 [pii]
AID - 10.1038/s41419-020-2457-5 [doi]
PST - epublish
SO  - Cell Death Dis. 2020 Apr 24;11(4):272. doi: 10.1038/s41419-020-2457-5.