ArticleThe Journal of biological chemistry2017
Pyruvate kinase M knockdown-induced signaling via AMP-activated protein kinase promotes mitochondrial biogenesis, autophagy, and cancer cell survival.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 78 citations in OpenAlex.
- LKB1 attenuates the transport activity of GLUT1 by regulating the alternative splicing of PKM1/PKM2 in cervical cancer.Journal of gynecologic oncology · 2026Article
- Targeting Pyruvate Kinase M2: Signal Transduction Pathways and Exploration of Cancer Therapeutic Strategies.The AAPS journal · 2026Review
- Glycolysis enzymes and cellular lactylation in tumour.Clinical and translational medicine · 2026Review
- Selective autophagic degradation of glycolytic activator PFKFB3 contributes to maintaining intestinal epithelial barrier in inflammatory bowel disease.International journal of molecular medicine · 2026Article
- Mechanical regulation of metabolism, epigenetics, and their interplay.npj biomedical innovations · 2026Review
- Targeted metabolism creates possibilities for lung cancer treatment in the precision tumor era.Respiratory research · 2026Review
- Oxidative and Glycolytic Metabolism: Their Reciprocal Regulation and Dysregulation in Cancer.Cells · 2025Review
- Gene therapy prevents onset of mitochondrial cardiomyopathy in neonatal mice with Ndufs6 deficiency.Cell death discovery · 2025Article
- Review
- [PKM1 Regulates the Expression of Autophagy and Neuroendocrine Markers in Small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2024Article
- Imbalance in Glucose Metabolism Regulates the Transition of Microglia from Homeostasis to Disease-Associated Microglia Stage 1.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- HPV18 oncoproteins driven expression of PKM2 reprograms HeLa cell metabolism to maintain aerobic glycolysis and viability.Virusdisease · 2022Article
- Impact of NSCLC metabolic remodeling on immunotherapy effectiveness.Biomarker research · 2022Review
- Pyruvate kinase M1 regulates butyrate metabolism in cancerous colonocytes.Scientific reports · 2022Article
- Correlation of Glucose Metabolism with Cancer and Intervention with Traditional Chinese Medicine.Evidence-based complementary and alternative medicine : eCAM · 2022Review
- Review
- Exercise prevents fatty liver by modifying the compensatory response of mitochondrial metabolism to excess substrate availability.Molecular metabolism · 2021Article
- Unfolding the role of autophagy in the cancer metabolism.Biochemistry and biophysics reports · 2021Article
- Pyruvate Kinase M2 Supports Muscle Progenitor Cell Proliferation but Is Dispensable for Skeletal Muscle Regeneration after Injury.The Journal of nutrition · 2021Article
- Long non-coding RNA SLC2A1-AS1 induced by GLI3 promotes aerobic glycolysis and progression in esophageal squamous cell carcinoma by sponging miR-378a-3p to enhance Glut1 expression.Journal of experimental & clinical cancer research : CR · 2021Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Preferential expression of the low-activity (dimeric) M2 isoform of pyruvate kinase (PK) over its constitutively active splice variant M1 isoform is considered critical for aerobic glycolysis in cancer cells. However, our results reported here indicate co-expression of PKM1 and PKM2 and their possible physical interaction in cancer cells. We show that knockdown of either PKM1 or PKM2 differentially affects net PK activity, viability, and cellular ATP levels of the lung carcinoma cell lines H1299 and A549. The stable knockdown of PK isoforms in A549 cells significantly reduced the cellular ATP level, whereas in H1299 cells the level of ATP was unaltered. Interestingly, the PKM1/2 knockdown in H1299 cells activated AMP-activated protein kinase (AMPK) signaling and stimulated mitochondrial biogenesis and autophagy to maintain energy homeostasis. In contrast, knocking down either of the PKM isoforms in A549 cells lacking LKB1, a serine/threonine protein kinase upstream of AMPK, failed to activate AMPK and sustain energy homeostasis and resulted in apoptosis. Moreover, in a similar genetic background of silenced PKM1 or PKM2, the knocking down of AMPKα1/2 catalytic subunit in H1299 cells induced apoptosis. Our findings help explain why previous targeting of PKM2 in cancer cells to control tumor growth has not met with the expected success. We suggest that this lack of success is because of AMPK-mediated energy metabolism rewiring, protecting cancer cell viability. On the basis of our observations, we propose an alternative therapeutic strategy of silencing either of the PKM isoforms along with AMPK in tumors.
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