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ELOVL5‐mediated fatty acid elongation promotes cellular proliferation and invasion in renal cell carcinoma
by
Nishiyama, Hiroyuki
, Kojima, Takahiro
, Matsuzaka, Takashi
, Siga, Masanobu
, Nagumo, Yoshiyuki
, Sakka, Shotaro
, Mathis, Bryan J.
, Shimazui, Toru
, Miyamoto, Takafumi
, Shimano, Hitoshi
, Negoro, Hiromitsu
, Kandori, Shuya
, Nitta, Satoshi
, Tanaka, Ken
in
Acetyltransferases - genetics
/ Acetyltransferases - metabolism
/ AKT protein
/ Apoptosis
/ Arachidonic acid
/ Carcinoma, Renal Cell - genetics
/ Carcinoma, Renal Cell - pathology
/ Cell proliferation
/ Cell Proliferation - genetics
/ cellular invasion
/ cellular proliferation
/ Chemokines
/ Chromatography
/ CRISPR
/ Design
/ Eicosapentaenoic acid
/ Elongation
/ elongation of very long–chain fatty acid 5
/ Endoplasmic reticulum
/ Experiments
/ Fatty Acid Elongases - genetics
/ Fatty Acids
/ Gene expression
/ Genomes
/ Humans
/ Kidney cancer
/ Kidney Neoplasms - genetics
/ Kidney Neoplasms - pathology
/ Laboratory animals
/ Lipid metabolism
/ Lipids
/ Liquid chromatography
/ Mass spectrometry
/ Mass spectroscopy
/ Medical prognosis
/ Metabolism
/ Metabolites
/ Original
/ ORIGINAL ARTICLES
/ Phosphorylation
/ polyunsaturated fatty acid
/ Polyunsaturated fatty acids
/ Proto-Oncogene Proteins c-akt
/ Renal cell carcinoma
/ Scientific imaging
/ Software
/ Stat3 protein
/ Statistical analysis
/ Supplements
/ Survival analysis
/ TOR protein
/ Tumors
/ Vascular endothelial growth factor
2022
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ELOVL5‐mediated fatty acid elongation promotes cellular proliferation and invasion in renal cell carcinoma
by
Nishiyama, Hiroyuki
, Kojima, Takahiro
, Matsuzaka, Takashi
, Siga, Masanobu
, Nagumo, Yoshiyuki
, Sakka, Shotaro
, Mathis, Bryan J.
, Shimazui, Toru
, Miyamoto, Takafumi
, Shimano, Hitoshi
, Negoro, Hiromitsu
, Kandori, Shuya
, Nitta, Satoshi
, Tanaka, Ken
in
Acetyltransferases - genetics
/ Acetyltransferases - metabolism
/ AKT protein
/ Apoptosis
/ Arachidonic acid
/ Carcinoma, Renal Cell - genetics
/ Carcinoma, Renal Cell - pathology
/ Cell proliferation
/ Cell Proliferation - genetics
/ cellular invasion
/ cellular proliferation
/ Chemokines
/ Chromatography
/ CRISPR
/ Design
/ Eicosapentaenoic acid
/ Elongation
/ elongation of very long–chain fatty acid 5
/ Endoplasmic reticulum
/ Experiments
/ Fatty Acid Elongases - genetics
/ Fatty Acids
/ Gene expression
/ Genomes
/ Humans
/ Kidney cancer
/ Kidney Neoplasms - genetics
/ Kidney Neoplasms - pathology
/ Laboratory animals
/ Lipid metabolism
/ Lipids
/ Liquid chromatography
/ Mass spectrometry
/ Mass spectroscopy
/ Medical prognosis
/ Metabolism
/ Metabolites
/ Original
/ ORIGINAL ARTICLES
/ Phosphorylation
/ polyunsaturated fatty acid
/ Polyunsaturated fatty acids
/ Proto-Oncogene Proteins c-akt
/ Renal cell carcinoma
/ Scientific imaging
/ Software
/ Stat3 protein
/ Statistical analysis
/ Supplements
/ Survival analysis
/ TOR protein
/ Tumors
/ Vascular endothelial growth factor
2022
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ELOVL5‐mediated fatty acid elongation promotes cellular proliferation and invasion in renal cell carcinoma
by
Nishiyama, Hiroyuki
, Kojima, Takahiro
, Matsuzaka, Takashi
, Siga, Masanobu
, Nagumo, Yoshiyuki
, Sakka, Shotaro
, Mathis, Bryan J.
, Shimazui, Toru
, Miyamoto, Takafumi
, Shimano, Hitoshi
, Negoro, Hiromitsu
, Kandori, Shuya
, Nitta, Satoshi
, Tanaka, Ken
in
Acetyltransferases - genetics
/ Acetyltransferases - metabolism
/ AKT protein
/ Apoptosis
/ Arachidonic acid
/ Carcinoma, Renal Cell - genetics
/ Carcinoma, Renal Cell - pathology
/ Cell proliferation
/ Cell Proliferation - genetics
/ cellular invasion
/ cellular proliferation
/ Chemokines
/ Chromatography
/ CRISPR
/ Design
/ Eicosapentaenoic acid
/ Elongation
/ elongation of very long–chain fatty acid 5
/ Endoplasmic reticulum
/ Experiments
/ Fatty Acid Elongases - genetics
/ Fatty Acids
/ Gene expression
/ Genomes
/ Humans
/ Kidney cancer
/ Kidney Neoplasms - genetics
/ Kidney Neoplasms - pathology
/ Laboratory animals
/ Lipid metabolism
/ Lipids
/ Liquid chromatography
/ Mass spectrometry
/ Mass spectroscopy
/ Medical prognosis
/ Metabolism
/ Metabolites
/ Original
/ ORIGINAL ARTICLES
/ Phosphorylation
/ polyunsaturated fatty acid
/ Polyunsaturated fatty acids
/ Proto-Oncogene Proteins c-akt
/ Renal cell carcinoma
/ Scientific imaging
/ Software
/ Stat3 protein
/ Statistical analysis
/ Supplements
/ Survival analysis
/ TOR protein
/ Tumors
/ Vascular endothelial growth factor
2022
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ELOVL5‐mediated fatty acid elongation promotes cellular proliferation and invasion in renal cell carcinoma
Journal Article
ELOVL5‐mediated fatty acid elongation promotes cellular proliferation and invasion in renal cell carcinoma
2022
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Overview
Renal cell carcinoma (RCC) features altered lipid metabolism and accumulated polyunsaturated fatty acids (PUFAs). Elongation of very long–chain fatty acid (ELOVL) family enzymes catalyze fatty acid elongation, and ELOVL5 is indispensable for PUFAs elongation, but its role in RCC progression remains unclear. Here, we show that higher levels of ELOVL5 correlate with poor RCC clinical prognosis. Liquid chromatography/electrospray ionization‐tandem mass spectrometry analysis showed decreases in ELOVL5 end products (arachidonic acid and eicosapentaenoic acid) under CRISPR/Cas9‐mediated knockout of ELOVL5 while supplementation with these fatty acids partially reversed the cellular proliferation and invasion effects of ELOVL5 knockout. Regarding cellular proliferation and invasion, CRISPR/Cas9‐mediated knockout of ELOVL5 suppressed the formation of lipid droplets and induced apoptosis via endoplasmic reticulum stress while suppressing renal cancer cell proliferation and in vivo tumor growth. Furthermore, CRISPR/Cas9‐mediated knockout of ELOVL5 inhibited AKT Ser473 phosphorylation and suppressed renal cancer cell invasion through chemokine (C‐C motif) ligand‐2 downregulation by AKT‐mTOR‐STAT3 signaling. Collectively, these results suggest that ELOVL5‐mediated fatty acid elongation promotes not only cellular proliferation but also invasion in RCC.
Elevated ELOVL5 expression is associated with poor renal cancer clinical prognosis. ELOVL5 promotes cellular proliferation by inhibiting apoptosis. ELOVL5 promotes cellular invasion via the AKT‐mTOR‐STAT3‐CCL2 signaling pathway.
Publisher
John Wiley & Sons, Inc,John Wiley and Sons Inc
Subject
/ Acetyltransferases - metabolism
/ Carcinoma, Renal Cell - genetics
/ Carcinoma, Renal Cell - pathology
/ Cell Proliferation - genetics
/ CRISPR
/ Design
/ elongation of very long–chain fatty acid 5
/ Fatty Acid Elongases - genetics
/ Genomes
/ Humans
/ Kidney Neoplasms - pathology
/ Lipids
/ Original
/ Proto-Oncogene Proteins c-akt
/ Software
/ Tumors
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