β-Arrestin 1 (ARRB1) has been known as a key negative regulator of G protein-coupled receptor signaling. During the past decade, it has been recognized that ARRB1 also functions as a signal transducer in its own right, by acting as an adaptor protein for various signaling pathways.
In this study, we report that ARRB1 plays essential roles in mediating gastric cancer cell metabolism and proliferation through binding with pyruvate kinase PKM2 and transcription factor E2F1, respectively, in distinct subcellular localizations by a time-dependent manner. Furthermore, the altered cell metabolism by the ARRB1–PKM2 axis could be reverted by the PKM2 activator DASA-58, providing an opportunity for therapeutic development to target metabolic vulnerability in gastric cancer cells.
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