TY - JOUR
T1 - Comparison of the ischemic and non-ischemic lung cancer metabolome reveals hyper activity of the TCA cycle and autophagy
AU - Kikuchi, Naohiko
AU - Soga, Tomoyoshi
AU - Nomura, Miyuki
AU - Sato, Taku
AU - Sakamoto, Yoshimi
AU - Tanaka, Ryota
AU - Abe, Jiro
AU - Morita, Mami
AU - Shima, Hiroshi
AU - Okada, Yoshinori
AU - Tanuma, Nobuhiro
N1 - Funding Information:
This work was supported by Grants from JSPS KAKENHI Grants ( 19H01036 to NT, 18K16433 to TS, and 18K15965 to MM), an AMED P-Create Grant (NT), the Takeda Science Foundation (NT), the Mochida Memorial Foundation for Medical and Pharmaceutical Research (MM), the Uehara Memorial Foundation (NT), the Naito Foundation (NT) and the Princess Takamatsu Cancer Research Fund (NT).
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/9/10
Y1 - 2020/9/10
N2 - 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.
AB - 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.
KW - Autophagy
KW - Cancer metabolism
KW - Ischemia
KW - Lung cancer
KW - Metabolome
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U2 - 10.1016/j.bbrc.2020.07.082
DO - 10.1016/j.bbrc.2020.07.082
M3 - Article
C2 - 32828300
AN - SCOPUS:85089476688
VL - 530
SP - 285
EP - 291
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 1
ER -