Emerging roles of AMPK signaling in gastrointestinal cancers: mechanistic insights and clinical prospects

AMP-activated protein kinase (AMPK) is a widely expressed energy and nutrient sensor in eukaryotic cells, playing a crucial role in regulating cellular energy homeostasis and various cellular metabolic processes. AMPK plays a complex role in the progression of gastrointestinal cancers, including hepatocellular carcinoma (HCC), gastric cancer (GC), and colorectal cancer (CRC), and exhibits both oncogenic and cancer-suppressive activities. On one hand, during the early stage of tumorigenesis, AMPK signaling can inhibit cancer cell proliferation and promote apoptosis, thereby exerting a protective effect. On the other hand, under hypoxic and nutrient-deficient conditions, AMPK may enhance the metabolic adaptability of cancer cells, thereby supporting cancer progression. This review summarizes the recent research progress on the upstream regulatory factors and downstream effector molecules of AMPK, discusses the unique role of AMPK in the regulation of gastrointestinal cancers, and proposes potential therapeutic strategies targeting AMPK.