Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

AMP-activated kinase (AMPK) is a central cellular energetic biosensor and regulator of a broad array of cellular metabolic routes activated by nutrient deprivation, mitochondrial dysfunction, oxidative stress, and cytokines. The activation of AMPK maintains ATP levels in response to hypoxia, mitochondrial dysfunction, and shortage of essential metabolic fuels. Activated AMPK turns on energy sparing pathways and promotes antiapoptotic functions thereby permitting cells to survive extremely hostile conditions for prolonged periods of time. Cancer cells in solid tumors are generally subjected to such harsh conditions; however, they manage to efficiently survive and proliferate. This is likely due, in great part, to a peculiar form of metabolism that is heavily reliant on glycolysis and which promotes cancer cell adaptation and tumor progression. AMPK controls the influx and utilization of glucose by cancer cells and therefore has emerged as an attractive target to treat cancer. Investigations exploring this possibility demonstrated that activators or inhibitors of AMPK impact cancer cell viability and possibly cancer progression. For example, the AMPK activator metformin induces apoptosis in a variety of cancer cell lines and models. A major problem with many of the studies on metformin is that little effort has been invested in unraveling how metformin activates AMPK in the many contexts it has been tested. This is significant because many AMPK-independent effects of metformin have been documented. The notion that AMPK acts solely as a tumor suppressor also conflicts with findings that it confers resistance to nutrient deprivation, sustains NADPH levels in cancer cells, facilitates stress-induced gene transcription, promotes cell survival via antiapoptotic function upregulation, intermediates epithelial-to-mesenchymal transition, and increases malignant transformation. These are all recognized steps necessary for the successful evolution of tumors. This review highlights some of these findings and proposes that the role of AMPK in cancer should be reconsidered in light of the complex roles of AMPK under different metabolic conditions.
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PMID:The multifaceted activities of AMPK in tumor progression--why the "one size fits all" definition does not fit at all? 2426 96

Manganese superoxide dismutase (MnSOD/SOD2) is a mitochondria-resident enzyme that governs the types of reactive oxygen species egressing from the organelle to affect cellular signalling. Here we demonstrate that MnSOD upregulation in cancer cells establishes a steady flow of H2O2 originating from mitochondria that sustains AMP-activated kinase (AMPK) activation and the metabolic shift to glycolysis. Restricting MnSOD expression or inhibiting AMPK suppresses the metabolic switch and dampens the viability of transformed cells indicating that the MnSOD/AMPK axis is critical to support cancer cell bioenergetics. Recapitulating in vitro findings, clinical and epidemiologic analyses of MnSOD expression and AMPK activation indicated that the MnSOD/AMPK pathway is most active in advanced stage and aggressive breast cancer subtypes. Taken together, our results indicate that MnSOD serves as a biomarker of cancer progression and acts as critical regulator of tumour cell metabolism.
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PMID:MnSOD upregulation sustains the Warburg effect via mitochondrial ROS and AMPK-dependent signalling in cancer. 2565 75

The gradual energy dissipation of all organisms allows adapting to energy demands. Pathological situations of uncured diseases such as cancer, diabetes, and other obesity-related diseases are caused by an abrupt energy imbalance. As an energy sensor, AMP-activated kinase (AMPK) can regulate the cellular energy status. In case of increased energy demands or insufficient nutrient supply, cells digest their own interior, which is called autophagy. AMPK-mediated autophagy regulates various metabolic and physiological processes and is dysregulated in different chronic conditions. Because of AMPK's critical role in physiology and pathology, it is an emerging target for both prevention and treatment of these uncured diseases. This review discusses the multifaceted role of AMPK on cancer cell survival and inhibition mechanism. First, we discuss the dual role of AMPK on cancer progression and suppression, and we discuss how different AMPK subunit combinations influence the tumor progression and suppression. Next, we discuss what could be the centering point of AMPK that supports promotion or inhibition of the cancer cell growth. Furthermore, we review the role of connecting mechanism of AMPK-mediated molecular intermediates on cancer cell survival and inhibition pathways. Finally, we discuss how AMPK can affect DNA damage and repairing mechanisms, and immune response of host cell and cancer cells.
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PMID:Role of AMPK and its molecular intermediates in subjugating cancer survival mechanism. 3100 18

Breast cancer is the most ubiquitous type of neoplasms among women worldwide. Molecular aberrations associated with breast development and progressions have been extensively investigated in recent years. An AMP-activated kinase (AMPK) initially identified as a cellular energy sensor that plays a crucial role in cellular energy homeostasis. Intensive research over the last decade about the molecular mechanisms of AMPK has demonstrated that AMPK mediated diverse biological functions are achieved through phosphorylation and regulation of multiple downstream signaling molecules in normal tissue. Downregulation of AMPK activity or decreased level involved in the promotion of breast tumorigenesis, and thus activation of AMPK found to oppose tumor progression. In this review, we epitomize the recent advances in exploring the tumor suppressor function of AMPK pathways. Besides, we discuss the developments in the area of AMPK activator and its molecular mechanisms for breast cancer treatment.
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PMID:Therapeutic aspects of AMPK in breast cancer: Progress, challenges, and future directions. 3243 11