Abstract 1542: Roles of extracellular ATP in inducing EMT and CSC-like changes to promote early steps of metastasis in non-small lung cancer cell lines

Abstract

Abstract Cancer is a major death-causing disease worldwide, and metastasis, a hallmark of cancer, is associated with up to 90% of all cancer-related deaths. Metastasis requires ATP, and the tumor microenvironment (TME) has much higher concentrations of intratumoral and extracellular ATP (eATP) than healthy tissue, implying that eATP may have potential roles in tumor development and progression. Our previous ATP studies, cited by a Nature Review Cancer paper in 20181 showed that eATP is internalized by cancer cell through macropinocytosis, and it promotes cancer cell growth, survival, and drug resistance. However, how intratumoral eATP plays roles in metastasis remains largely unclear. Our 2019 published results show that eATP promotes cancer migration and invasion, initiates epithelial to mesenchymal transition (EMT), alters expression level of EMT related protein markers such as ZEB1, SNAIL, SLUG in human non-small lung cancer cell (NSCLC) lines2. It has been reported that the EMT and cancer stem cells (CSCs) share some molecular links, but the detailed mechanisms involved are still unknown. Recently, we have found the eATP significantly induces the gene expression level of CSC transcription factors (TFs): SOX2, NANOG and OCT4 in A549 cells in a time-dependent manner. We have also found that, after A549 cells were pretreated with 0.5mM for 6 hrs, the ATP-pretreated A549 cells were able to show significantly increased migration and invasion even in the absence of ATP addition. Based on all these results, we hypothesize that extracellular ATP functions as a messenger, a signal facilitator, an energy molecule, and a transcription cofactor to induce EMT and CSC-like features to promote metastasis in NSCLC. RNAseq and metabolomics studies are being used to determine the transcriptional and metabolic changes associated with the ATP induced EMT and CSC process in NSCLC. The completion of the project will not only unravel eATP's roles in EMT and CSC induction and early steps of tumor metastasis, but also potentially provide novel promising therapeutic targets for inhibiting tumor metastasis. Citation Format: Jingwen Song, Maria Evers, Xiaozhuo Chen. Roles of extracellular ATP in inducing EMT and CSC-like changes to promote early steps of metastasis in non-small lung cancer cell lines [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1542.