The LKB1-AMPK pathway is a novel signaling pathway that links cell metabolism to growth control and cell polarity. LKB1, a serine/threonine kinase, directly phosphorylates and activates AMPK, which regulates lipid, cholesterol, and glucose metabolism in specialized metabolic tissues. The connection between AMPK and tumor suppressors suggests that therapeutic manipulation of this pathway with established diabetes drugs may warrant further investigation in cancer therapy. LKB1 acts as a master upstream kinase, activating AMPK and a family of 12 related kinases involved in cell growth, metabolism, and polarity. The LKB1-AMPK pathway serves as a metabolic checkpoint, arresting cell growth under conditions of low ATP. One of the central mitogenic pathways suppressed by LKB1 and AMPK signaling is the mTORC1 pathway, which is inhibited by AMPK phosphorylation of TSC2 and raptor. Organismal metabolism and overnutrition can suppress LKB1-AMPK signaling, contributing to increased cancer risk in obese or diabetic patients. Conversely, activation of LKB1/AMPK signaling may contribute to the suppression of cancer risk associated with exercise and caloric restriction. AMPK has also been shown to regulate other key cancer-related pathways, including p53 and the Wnt signaling pathway. LKB1-dependent kinases may control cell growth and metabolism through phosphorylation of transcriptional coactivators. LKB1 and AMPK have been implicated in cell polarity, and their loss can lead to polarity defects during embryogenesis and oogenesis. Genetic studies on LKB1 loss in mice have revealed a number of cancerous phenotypes, including gastrointestinal polyposis and various types of cancers. AMPK agonists, such as metformin, have shown promise as cancer therapeutics, and epidemiological studies suggest a potential tumor suppressive effect of prolonged use. However, further research is needed to fully understand the mechanisms and therapeutic potential of AMPK activation in cancer treatment.The LKB1-AMPK pathway is a novel signaling pathway that links cell metabolism to growth control and cell polarity. LKB1, a serine/threonine kinase, directly phosphorylates and activates AMPK, which regulates lipid, cholesterol, and glucose metabolism in specialized metabolic tissues. The connection between AMPK and tumor suppressors suggests that therapeutic manipulation of this pathway with established diabetes drugs may warrant further investigation in cancer therapy. LKB1 acts as a master upstream kinase, activating AMPK and a family of 12 related kinases involved in cell growth, metabolism, and polarity. The LKB1-AMPK pathway serves as a metabolic checkpoint, arresting cell growth under conditions of low ATP. One of the central mitogenic pathways suppressed by LKB1 and AMPK signaling is the mTORC1 pathway, which is inhibited by AMPK phosphorylation of TSC2 and raptor. Organismal metabolism and overnutrition can suppress LKB1-AMPK signaling, contributing to increased cancer risk in obese or diabetic patients. Conversely, activation of LKB1/AMPK signaling may contribute to the suppression of cancer risk associated with exercise and caloric restriction. AMPK has also been shown to regulate other key cancer-related pathways, including p53 and the Wnt signaling pathway. LKB1-dependent kinases may control cell growth and metabolism through phosphorylation of transcriptional coactivators. LKB1 and AMPK have been implicated in cell polarity, and their loss can lead to polarity defects during embryogenesis and oogenesis. Genetic studies on LKB1 loss in mice have revealed a number of cancerous phenotypes, including gastrointestinal polyposis and various types of cancers. AMPK agonists, such as metformin, have shown promise as cancer therapeutics, and epidemiological studies suggest a potential tumor suppressive effect of prolonged use. However, further research is needed to fully understand the mechanisms and therapeutic potential of AMPK activation in cancer treatment.