期刊
CANCER LETTERS
卷 351, 期 2, 页码 242-251出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2014.06.008
关键词
Warburg effect; Cancer metabolism; Nonhydrolyzable fluorescent ATP; Receptor tyrosine kinase; Kras
类别
资金
- State of Ohio
- Donald Clippinger Graduate Fellowship
- Graduate Student Senate Original Work Grant from Ohio University
- AACR-WICR Scholar Award
- Student Enhance Award
ATP plays central roles in cancer metabolism and the Warburg effect. Intratumoral ATP concentrations are up to 10(4) times higher than those of interstitial ATP in normal tissues. However, extracellular ATP is not known to enter cancer cells. Here we report that human A549 lung cancer cells internalized extracellular ATP by macropinocytosis as demonstrated by colocalization of a nonhydrolyzable fluorescent ATP and a macropinocytosis tracer high-molecular-weight dextran, as well as by a macropinocytosis inhibitor study. Extracellular ATP also induced increase of intracellular ATP levels, without involving transcription and translation at significant levels, and cancer cells' resistance to ATP-competitor anticancer drugs, likely through the mechanism of ATP internalization. These findings, described for the first time, have profound implications in ATP-sharing among cancer cells in tumors and highlight a novel anticancer target. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
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