Open AccessStearate‐to‐palmitate ratio modulates endoplasmic reticulum stress and cell apoptosis in non‐B non‐C hepatoma cells
Author(s) -
Shibasaki Yasushi,
Horikawa Makoto,
Ikegami Koji,
Kiuchi Ryota,
Takeda Makoto,
Hiraide Takanori,
Morita Yoshifumi,
Konno Hiroyuki,
Takeuchi Hiroya,
Setou Mitsutoshi,
Sakaguchi Takanori
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13529
Subject(s) - endoplasmic reticulum , steatohepatitis , fatty liver , apoptosis , downregulation and upregulation , hepatocellular carcinoma , intracellular , unfolded protein response , chemistry , fatty acid metabolism , microbiology and biotechnology , endocrinology , cancer research , medicine , biochemistry , metabolism , biology , gene , disease
The increased prevalence of hepatocellular carcinoma ( HCC ) without viral infection, namely, NHCC , is a major public health issue worldwide. NHCC is frequently derived from non‐alcoholic fatty liver ( NAFL ) and non‐alcoholic steatohepatitis, which exhibit dysregulated fatty acid ( FA ) metabolism. This raises the possibility that NHCC evolves intracellular machineries to adapt to dysregulated FA metabolism. We herein aim to identify NHCC ‐specifically altered FA and key molecules to achieve the adaptation. To analyze FA , imaging mass spectrometry ( IMS ) was performed on 15 HCC specimens. The composition of saturated FA ( SFA ) in NHCC was altered from that in typical HCC . The stearate‐to‐palmitate ratio ( SPR ) was significantly increased in NHCC . Associated with the SPR increase, the ELOVL 6 protein level was upregulated in NHCC . The knockdown of ELOVL 6 reduced SPR , and enhanced endoplasmic reticulum stress, inducing apoptosis of Huh7 and HepG2 cells. In conclusion, NHCC appears to adapt to an FA ‐rich environment by modulating SPR through ELOVL 6.