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

• Published in: Biochemical and biophysical research communications 2020-09, Vol.530 (1), p.285-291
• Main Authors: Kikuchi, Naohiko, Soga, Tomoyoshi, Nomura, Miyuki, Sato, Taku, Sakamoto, Yoshimi, Tanaka, Ryota, Abe, Jiro, Morita, Mami, Shima, Hiroshi, Okada, Yoshinori, Tanuma, Nobuhiro
• Format: Article
• Language: English
• Subjects: Animals; Autophagy; Autophagy-Related Protein 7 - genetics; Autophagy-Related Protein 7 - metabolism; Cancer metabolism; Cell Line, Tumor; Citric Acid Cycle; Female; Gene Deletion; Ischemia; Ischemia - etiology; Ischemia - genetics; Ischemia - metabolism; Ischemia - pathology; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Lung Neoplasms - surgery; Metabolome; Mice
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2020.07.082

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. •Different surgical procedures alter the lung cancer metabolome in vivo.•Tissues removed by lobectomy specifically underwent ischemia.•Responses to ischemia reveal high TCA cycle and autophagic activity of tumors.•Autophagy confers metabolic advantages to lung cancer cells.