Open AccessAdenosine interaction with adenosine receptor A2a promotes gastric cancer metastasis by enhancing PI3K–AKT–mTOR signaling
Author(s) -
Li Shi,
Zhaoying Wu,
Ji Miao,
Shangce Du,
Shichao Ai,
En Xu,
Min Feng,
Jun Song,
Wei Guan
Publication year - 2019
Publication title -
molecular biology of the cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.463
H-Index - 225
eISSN - 1939-4586
pISSN - 1059-1524
DOI - 10.1091/mbc.e19-03-0136
Subject(s) - pi3k/akt/mtor pathway , biology , adenosine , protein kinase b , cancer research , metastasis , signal transduction , microbiology and biotechnology , cancer , endocrinology , genetics
The accumulation of adenosine in the tumor microenvironment is associated with tumor progression in many cancers. However, whether adenosine is involved in gastric cancer (GC) metastasis and progression, and the underlying molecular mechanism, is largely unclear. In this study, we find that GC tissues and cell lines had higher A2aR levels than nontumor gastric tissues and cell lines. A2aR expression correlated positively with TNMstage, and associated with poor outcomes. Adenosine enhanced the expression of the stemness and epithelial–mesenchymal transition-associated genes by binding to A2aR. A2aR expression on GC cells promoted metastasis in vivo. The PI3K-AKT-mTOR signaling pathway was involved in adenosine-stimulated GC cell migration and invasion. Our results indicate that adenosine promotes GC cell invasion and metastasis by interacting with A2aR to enhance PI3K–AKT–mTOR pathway signaling.