Comparison of the ischemic and non-ischemic lung cancer metabolome reveals hyper activity of the TCA cycle and autophagy.
Comparison of the ischemic and non-ischemic lung cancer metabolome reveals hyper activity of the TCA cycle and autophagy.
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DOI：
10.1016/j.bbrc.2020.07.082
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发表时间：
2020-09
影响因子：
3.1
通讯作者：
N. Kikuchi;T. Soga;Miyuki Nomura;Taku Sato;Yoshimi Sakamoto;R. Tanaka;Jiro Abe;Mami Morita;H. Shima;Y. Okada;N. Tanuma
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文献类型：
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作者：
N. Kikuchi;T. Soga;Miyuki Nomura;Taku Sato;Yoshimi Sakamoto;R. Tanaka;Jiro Abe;Mami Morita;H. Shima;Y. Okada;N. Tanuma
癌症生物学的最新进展揭示了代谢变化在癌症中的重要性；然而，关于肿瘤代谢途径是如何在体内调节的，我们所知甚少。在这里，我们报告了基于不同手术方式的肺癌代谢分析，即肺叶切除术和部分切除术。在肺叶切除术中，而不是部分切除，在切除组织之前结扎肺动脉和肺静脉，使组织缺血。我们发现肿瘤在肺叶切除术后确实经历了缺血，并且肿瘤代谢组与部分切除肿瘤的代谢组明显不同。比较肿瘤组织和正常肺组织对缺血的反应，发现肺癌组织比正常肺组织表现出更强的TCA循环和自噬活性。最后，我们报道，删除编码自噬必需蛋白的atg7，可以拮抗肺癌细胞系衍生的肿瘤生长，这表明自噬赋予肺癌代谢优势。我们的研究结果揭示了肿瘤和正常组织对缺血的不同代谢反应。
Recent advances in cancer biology reveal the importance of metabolic changes in cancer; however, less is known about how metabolic pathways in tumors are regulatedin 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 tissuesin vivoin patients. Finally, we report that deletingATG7, 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.