DAPk and pyruvate kinase: Unlikely partners in cancer metabolic regulation

Mor, Inbal; Bialik, Shani; Kimchi, Adi

doi:10.4161/cc.11.1.18653

Cited by 2 publications

(2 citation statements)

References 11 publications

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“…Thus, DAPK impedes unregulated cell proliferation, which is consistent with its tumor suppressive activity. 10,12 with the loss of p53-directed suppression on PGM and Oct1, 22 PEP accumulation converts PGM into a lactate-producing enzyme, allowing high rate of glycolysis to support the anabolic metabolism. 38,39 ROS-mediated redox potential also has a role in the regulation of the TSC-Rheb-mTORC1 pathway.…”

Section: Dapk Activity For Normal Proliferationmentioning

confidence: 99%

“…33 Thus, during cellular transformation, loss or functional alterations in DAPK activity could convert a death-inducing signal into a pro-survival signal. 12,14 DAPK inactivation reduces the induction of p19 ARF / p53-dependent pathway for apoptosis. 33 Therefore, one of the outcomes of loss of DAPK in cancer development may involve the attenuation of the p19 ARF /p53 dependent pro-apoptotic signals triggered by oncogenes like cMyc and E2F1.…”

Section: Dapk Activity For Normal Proliferationmentioning

confidence: 99%

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Death-associated proliferation kinetic in normal and transformed cells

Erol¹

2012

Cell Cycle

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Pyruvate kinase M2 (PKM2) may occur in both a tetrameric and a dimeric form. When the majority of PKM2 molecules are in the highly active tetrameric conformation, glucose is primarily degraded to pyruvate and lactate with the regeneration of energy. A tumor suppressor protein, death-associated protein kinase (DAPK), interacts with PKM2 protein and stabilizes PKM2 in its active tetrameric form in normal proliferating cells. However, DAPK is widely inactivated in cancer cells, leading to the loss of the active conformation of PKM2. This may render PKM2 sensitive to cellular oxidants, switching the enzyme into its inactive dimeric form. Consequently, inhibition of PKM2 after oxidative stress contributes optimal tumor growth and allows cancer cells to withstand oxidative stress.

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Section: Dapk Activity For Normal Proliferationmentioning

confidence: 99%

Section: Dapk Activity For Normal Proliferationmentioning

confidence: 99%

Death-associated proliferation kinetic in normal and transformed cells

Erol¹

2012

Cell Cycle

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Molecular Pathways: Preclinical Models and Clinical Trials with Metformin in Breast Cancer

Thompson

2014

Clinical Cancer Research

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Metformin, an oral biguanide widely used to treat diabetes, has considerable potential and is in clinical trials as an experimental preventive or therapeutic agent for a range of cancers. Direct actions targeting cellular pathways, particularly via AMP-activated protein kinase and through inhibiting mitochondrial ATP synthesis, or systemic mechanisms involving insulin and insulin-like growth factors have been much studied in vitro and in preclinical models. Epidemiologic and retrospective studies also provide clinical evidence in support of metformin as an antitumor agent. Preoperative window-ofopportunity trials confirm the safety of metformin in women with primary breast cancer, and demonstrate reduction in tumor cell proliferation and complex pathways of gene suppression or overexpression attributable to metformin. Confirmation of insulin-mediated effects, independent of body mass index, also supports the potential benefit of adjuvant metformin therapy. Neoadjuvant, adjuvant, and advanced disease trials combining metformin with established anticancer agents are under way or proposed. Companion biomarker studies will utilize in vitro and preclinical understanding of the relevant molecular pathways to, in future, refine patient and tumor selection for metformin therapy. Clin Cancer Res; 20(10); 2508-15. Ó2014 AACR.

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DAPk and pyruvate kinase: Unlikely partners in cancer metabolic regulation

Cited by 2 publications

References 11 publications

Death-associated proliferation kinetic in normal and transformed cells

Death-associated proliferation kinetic in normal and transformed cells

Molecular Pathways: Preclinical Models and Clinical Trials with Metformin in Breast Cancer

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