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STK11/LKB1, is an essential human tumor suppressor, the key upstream activator of the AMP-activated protein kinase (AMPK). AMPK is a central metabolic switch found in all eukaryotes that govern glucose and lipid metabolism in response to alterations in nutrients and intracellular energy levels. LKB1 and AMPK control cell growth in response to environmental nutrient changes. One of the major growth regulatory pathways controlled by LKB1-AMPK is the mammalian target-of-rapamycin (mTOR) pathway. mTOR is a central integrator of nutrient and growth factors that control cell growth in all eukaryotes and is deregulated in human cancers.
STK11/LKB1 must activate AMPK to turn down mTOR (growth). A loss of function mutation in LKB1 leads to inadequate activation of AMPK and subsequently mTOR remains elevated, leading to aberrant cell growth; a known cause for many diseases including PJS, Lung Cancer, Tuberous Sclerosis, Pancreatic Cancer, Breast Cancer, Stomach Cancer, Small intestine Cancer, Cervical Cancer, Uterine Cancer, Testicular Cancer, Esophageal Cancer, Alzheimer's disease, Cowden Syndrome, Bannayan-Riley-Ruvalcaba Syndrome, Lhermitte-Duclos disease, Proteus Syndrome, Polycystic Kidney disease, Obesity & Type 2 Diabetes, Cardiac Hypertrophy, Cardiovascular disease, Proteus Syndrome.
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