Comparison of the ischemic and non-ischemic lung cancer metabolome reveals hyper activity of the TCA cycle and autophagy

Naohiko Kikuchi, Tomoyoshi Soga, Miyuki Nomura, Taku Sato, Yoshimi Sakamoto, Ryota Tanaka, Jiro Abe, Mami Morita, Hiroshi Shima, Yoshinori Okada, Nobuhiro Tanuma

Research output: Contribution to journalArticlepeer-review

Abstract

Recent advances in cancer biology reveal the importance of metabolic changes in cancer; however, less is known about how metabolic pathways in tumors are regulated in vivo. Here, we report analysis of the lung cancer metabolism based on different surgical procedures, namely lobectomy and partial resection. In lobectomy, but not in partial resection, pulmonary arteries and veins are ligated prior to removal of tissues, rendering tissues ischemic. We show that tumors indeed undergo ischemia upon lobectomy and that the tumor metabolome differs markedly from that of tumors removed by partial resection. Comparison of the responses to ischemia in tumor and normal lung tissues revealed that lung cancer tissue exhibits greater TCA cycle and autophagic activity than do normal lung tissues in vivo in patients. Finally, we report that deleting ATG7, which encodes a protein essential for autophagy, antagonizes growth of tumors derived from lung cancer cell lines, suggesting that autophagy confers metabolic advantages to lung cancer. Our findings shed light on divergent metabolic responses to ischemia seen in tumors and normal tissues.

Original languageEnglish
Pages (from-to)285-291
Number of pages7
JournalBiochemical and biophysical research communications
Volume530
Issue number1
DOIs
Publication statusPublished - 2020 Sep 10

Keywords

  • Autophagy
  • Cancer metabolism
  • Ischemia
  • Lung cancer
  • Metabolome

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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