An integrative pan-cancer investigation reveals common genetic and transcriptional alterations of AMPK pathway genes as important predictors of clinical outcomes across major cancer types

Lai, Alvina G.

doi:10.1186/s12885-020-07286-2

Cited by 13 publications

(9 citation statements)

References 60 publications

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“…The activation of STK11 could also be involved in the activation of phosphofructokinase 1 (PFK1) and PFK2, which are part of the glycolysis process [ 37 ]. These proteins and the AMPK pathway are of particular interest because of their involvement in cancer multidrug resistance and their use for the prediction of clinical outcome of major cancer types [ 38 ].…”

Section: Resultsmentioning

confidence: 99%

Cytotoxic Fractions from Hechtia glomerata Extracts and p-Coumaric Acid as MAPK Inhibitors

et al. 2021

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Preliminary bioassay-guided fractionation was performed to identify cytotoxic compounds from Hechtia glomerata, a plant that is used in Mexican ethnomedicine. Organic and aqueous extracts were prepared from H. glomerata’s leaves and evaluated against two cancer cell lines. The CHCl3/MeOH (1:1) active extract was fractionated, and the resulting fractions were assayed against prostate adenocarcinoma PC3 and breast adenocarcinoma MCF7 cell lines. Active fraction 4 was further analyzed by high-performance liquid chromatography–quadrupole time-of-flight–mass spectrometry analysis to identify its active constituents. Among the compounds that were responsible for the cytotoxic effects of this fraction were flavonoids, phenolic acids, and aromatic compounds, of which p-coumaric acid (p-CA) and its derivatives were abundant. To understand the mechanisms that underlie p-CA cytotoxicity, a microarray assay was performed on PC3 cells that were treated or not with this compound. The results showed that mitogen-activated protein kinases (MAPKs) that regulate many cancer-related pathways were targeted by p-CA, which could be related to the reported effects of reactive oxygen species (ROS). A molecular docking study of p-CA showed that this phenolic acid targeted these protein active sites (MAPK8 and Serine/Threonine protein kinase 3) at the same binding site as their inhibitors. Thus, we hypothesize that p-CA produces ROS, directly affects the MAPK signaling pathway, and consequently causes apoptosis, among other effects. Additionally, p-CA could be used as a platform for the design of new MAPK inhibitors and re-sensitizing agents for resistant cancers.

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Section: Resultsmentioning

confidence: 99%

Cytotoxic Fractions from Hechtia glomerata Extracts and p-Coumaric Acid as MAPK Inhibitors

et al. 2021

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“…There are numerous pre-clinical evidences stating the dual nature of AMPK in cancer. However, the controversy over the positive and negative regulatory effects of AMPK in the context of cancer cannot Frontiers in Immunology frontiersin.org be resolved without substantial clinical evidence (126). The research pertaining to the clinical outcomes of differential regulation of AMPK signaling in cancer is still in a nascent stage.…”

Section: Limitations and Future Perspectivesmentioning

confidence: 99%

“…The aforementioned data indicates that the pro- or anti-tumorigenic roles of AMPK are likely to be dependent on the levels of the nutrients in the TME ( 125 ). Notably, another independent study involving a pan-cancer analysis using multi-omics approach reveals that genetic as well as transcriptional aberrations in AMPK signaling elicits tissue-dependent pro- or anti-tumor impacts across major cancer types ( 126 ).…”

Section: The Pro-tumorigenic Functions Of Ampk: Double-edged Sword In...mentioning

confidence: 99%

The role of AMPK in cancer metabolism and its impact on the immunomodulation of the tumor microenvironment

et al. 2023

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Adenosine monophosphate-activated protein kinase (AMPK) is a key metabolic sensor that is pivotal for the maintenance of cellular energy homeostasis. AMPK contributes to diverse metabolic and physiological effects besides its fundamental role in glucose and lipid metabolism. Aberrancy in AMPK signaling is one of the determining factors which lead to the development of chronic diseases such as obesity, inflammation, diabetes, and cancer. The activation of AMPK and its downstream signaling cascades orchestrate dynamic changes in the tumor cellular bioenergetics. It is well documented that AMPK possesses a suppressor role in the context of tumor development and progression by modulating the inflammatory and metabolic pathways. In addition, AMPK plays a central role in potentiating the phenotypic and functional reprogramming of various classes of immune cells which reside in the tumor microenvironment (TME). Furthermore, AMPK-mediated inflammatory responses facilitate the recruitment of certain types of immune cells to the TME, which impedes the development, progression, and metastasis of cancer. Thus, AMPK appears to play an important role in the regulation of anti-tumor immune response by regulating the metabolic plasticity of various immune cells. AMPK effectuates the metabolic modulation of anti-tumor immunity via nutrient regulation in the TME and by virtue of its molecular crosstalk with major immune checkpoints. Several studies including that from our lab emphasize on the role of AMPK in regulating the anticancer effects of several phytochemicals, which are potential anticancer drug candidates. The scope of this review encompasses the significance of the AMPK signaling in cancer metabolism and its influence on the key drivers of immune responses within the TME, with a special emphasis on the potential use of phytochemicals to target AMPK and combat cancer by modulating the tumor metabolism.

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“…However, some studies demonstrated that the abnormal expression and activation of AMPK in cancer cells plays an important role in promoting proliferation, metastasis, and maintaining cancer cell survival under stress conditions [ 23 , 24 , 25 ]. A study investigating 92 pathway genes of AMPK in 21 types of cancers indicated opposite effects of AMPK on cancer progression [ 26 ]. Therefore, biomolecules in cancer cells and pharmacological modulators, including metformin, tamoxifen, as well as some other natural products, can manage cancer progression by regulating activities of AMPK and its downstream targets.…”

Section: Introductionmentioning

confidence: 99%

Novel Anti-Cancer Products Targeting AMPK: Natural Herbal Medicine against Breast Cancer

et al. 2023

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Breast cancer is a common cancer in women worldwide. The existing clinical treatment strategies have been able to limit the progression of breast cancer and cancer metastasis, but abnormal metabolism, immunosuppression, and multidrug resistance involving multiple regulators remain the major challenges for the treatment of breast cancer. Adenosine 5′-monophosphate (AMP)-Activated Protein Kinase (AMPK) can regulate metabolic reprogramming and reverse the “Warburg effect” via multiple metabolic signaling pathways in breast cancer. Previous studies suggest that the activation of AMPK suppresses the growth and metastasis of breast cancer cells, as well as stimulating the responses of immune cells. However, some other reports claim that the development and poor prognosis of breast cancer are related to the overexpression and aberrant activation of AMPK. Thus, the role of AMPK in the progression of breast cancer is still controversial. In this review, we summarize the current understanding of AMPK, particularly the comprehensive bidirectional functions of AMPK in cancer progression; discuss the pharmacological activators of AMPK and some specific molecules, including the natural products (including berberine, curcumin, (−)-epigallocatechin-3-gallate, ginsenosides, and paclitaxel) that influence the efficacy of these activators in cancer therapy; and elaborate the role of AMPK as a potential therapeutic target for the treatment of breast cancer.

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An integrative pan-cancer investigation reveals common genetic and transcriptional alterations of AMPK pathway genes as important predictors of clinical outcomes across major cancer types

Cited by 13 publications

References 60 publications

Cytotoxic Fractions from Hechtia glomerata Extracts and p-Coumaric Acid as MAPK Inhibitors

Cytotoxic Fractions from Hechtia glomerata Extracts and p-Coumaric Acid as MAPK Inhibitors

The role of AMPK in cancer metabolism and its impact on the immunomodulation of the tumor microenvironment

Novel Anti-Cancer Products Targeting AMPK: Natural Herbal Medicine against Breast Cancer

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