Abstract
Mammalian target of rapamycin (mTOR) is aberrantly activated in many cancer types, and two rapamycin derivatives are currently approved by the Food and Drug Administration (FDA) of the United States for treating renal cell carcinoma. Mechanistically, mTOR is hyperactivated in human cancers either due to the genetic activation of its upstream activating signaling pathways or the genetic inactivation of its negative regulators. The tumor suppressor liver kinase B1 (LKB1), also known as serine/threonine kinase 11 (STK11), is involved in cell polarity, cell detachment and adhesion, tumor metastasis, and energetic stress response. A key role of LKB1 is to negatively regulate the activity of mTOR complex 1 (mTORC1). This review summarizes the molecular basis of this negative interaction and recent research progress in this area.
Publication types
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Research Support, N.I.H., Extramural
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Review
MeSH terms
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AMP-Activated Protein Kinase Kinases
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AMP-Activated Protein Kinases / metabolism
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Adenocarcinoma / drug therapy
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Adenocarcinoma / metabolism
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Animals
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Antibiotics, Antineoplastic / therapeutic use
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Disease Models, Animal
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Endometrial Neoplasms / drug therapy
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Endometrial Neoplasms / metabolism
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Female
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Humans
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Mechanistic Target of Rapamycin Complex 1
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Multiprotein Complexes / metabolism
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Phosphatidylinositol 3-Kinases / metabolism
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Protein Serine-Threonine Kinases / metabolism*
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Proto-Oncogene Proteins c-akt / metabolism
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Signal Transduction*
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Sirolimus / therapeutic use
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TOR Serine-Threonine Kinases / metabolism*
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Tuberous Sclerosis Complex 1 Protein
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Tuberous Sclerosis Complex 2 Protein
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Tumor Suppressor Proteins / metabolism
Substances
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Antibiotics, Antineoplastic
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Multiprotein Complexes
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Tuberous Sclerosis Complex 1 Protein
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Tuberous Sclerosis Complex 2 Protein
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Tumor Suppressor Proteins
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MTOR protein, human
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Mechanistic Target of Rapamycin Complex 1
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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STK11 protein, human
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TOR Serine-Threonine Kinases
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AMP-Activated Protein Kinase Kinases
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AMP-Activated Protein Kinases
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Sirolimus