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.
Highlights
Metabolic abnormality is regarded as an important feature of tumors which could help to adjust the microenvironment to meet the requirement of constantgrowing tumor cells
Fatty acid desaturase 1 (FADS1) is upregulated in Laryngeal squamous cell carcinoma (LSCC) tissues The expression and clinical significance of FADS1 were assessed by GEPIA based on high-throughput RNAsequencing data of HNSC cohort of the TCGA database
We further evaluated the relationship between FADS1 expression level and each clinicopathological factor in LSCC paraffin specimens
Summary
Metabolic abnormality is regarded as an important feature of tumors which could help to adjust the microenvironment to meet the requirement of constantgrowing tumor cells. Laryngeal squamous cell carcinoma (LSCC) accounts for ~90% of larynx cancer[23], which is the second most prevalent malignancy occurred in head and neck as well as respiratory tract with high incidence and mortality rate[24,25,26]. The malignant progression of LSCC initiates from a common type of premalignant lesion called laryngeal severe dysplasia. Poor living habits such as imbalanced diet including dietary fat, smoking and alcohol consumption, are the main risk factors contributed to the incidence of laryngeal cancer[27,28]. In this study, we performed in vitro and in vivo assays, and identified that FADS1, as a main mediator of PUFAs, played an oncogenic role in the progression of laryngeal cancer by activating the AKT/ mTOR signaling
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