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FADS1 promotes the progression of laryngeal squamous cell carcinoma through activating AKT/mTOR signaling.

ABSTRACT: 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 (PGE₂), 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.

SUBMITTER: Zhao R

PROVIDER: S-EPMC7181692 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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FADS1 promotes the progression of laryngeal squamous cell carcinoma through activating AKT/mTOR signaling.

Zhao Rui R Tian Linli L Zhao Bo B Sun Yanan Y Cao Jing J Chen Kexin K Li Fengqing F Li Minghua M Shang Desi D Liu Ming M

Cell death & disease 20200424 4

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 prognos ...[more]

PMID: 32332698

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FADS1 promotes the progression of laryngeal squamous cell carcinoma through activating AKT/mTOR signaling.

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FADS1 promotes the progression of laryngeal squamous cell carcinoma through activating AKT/mTOR signaling.

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