ELOVL5‐mediated fatty acid elongation promotes cellular proliferation and invasion in renal cell carcinoma

• DOI: 10.1111/cas.15454
• Publication Date: 2022-06-07T07:16:39Z
• Authors: Satoshi Nitta; Shuya Kandori; Ken Tanaka; Shotaro Sakka; Masanobu Siga; Yoshiyuki Nagumo; Hiromitsu Negoro; Takahiro Kojima; Bryan J. Mathis; Toru Shimazui; Takafumi Miyamoto; Takashi Matsuzaka; Hitoshi Shimano; Hiroyuki Nishiyama
• Keywords: 0301 basic medicine; 03 medical and health sciences; Acetyltransferases; Fatty Acid Elongases; Fatty Acids; Humans; ORIGINAL ARTICLES; Carcinoma, Renal Cell; Proto-Oncogene Proteins c-akt; Kidney Neoplasms; Cell Proliferation; 3. Good health

Renal cell carcinoma (RCC) features altered lipid metabolism and accumulated polyunsaturated fatty acids (PUFAs). Elongation of very long-chain acid (ELOVL) family enzymes catalyze elongation, ELOVL5 is indispensable for PUFAs but its role in RCC progression remains unclear. Here, we show that higher levels correlate with poor clinical prognosis. Liquid chromatography/electrospray ionization-tandem mass spectrometry analysis showed decreases end products (arachidonic eicosapentaenoic acid) under CRISPR/Cas9-mediated knockout while supplementation these partially reversed the cellular proliferation invasion effects knockout. Regarding invasion, suppressed formation droplets induced apoptosis via endoplasmic reticulum stress suppressing renal cancer vivo tumor growth. Furthermore, inhibited AKT Ser473 phosphorylation through chemokine (C-C motif) ligand-2 downregulation by AKT-mTOR-STAT3 signaling. Collectively, results suggest ELOVL5-mediated elongation promotes not only also RCC.