Hedgehog Interacting Protein (HHIP) Represses Airway Remodeling and Metabolic Reprogramming in COPD-Derived Airway Smooth Muscle Cells

Researchers suggest that HHIP repressed aerobic glycolysis and airway smooth muscle cells hyperplasia, which might contribute to the increased airway remodeling in Hhip+/- mice.
[Scientific Reports]
Li, Y., Zhang, L., Polverino, F., Guo, F., Hao, Y., Lao, T., Xu, S., Li, L., Pham, B., Owen, C. A., & Zhou, X. (2021). Hedgehog interacting protein (HHIP) represses airway remodeling and metabolic reprogramming in COPD-derived airway smooth muscle cells. Scientific Reports, 11(1), 9074. https://doi.org/10.1038/s41598-021-88434-x Cite
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The Role of PKM2 Nuclear Translocation in the Constant Activation of the NF-κB Signaling Pathway in Cancer-Associated Fibroblasts

The authors showed that mesenchymal stem cells differentiated into cancer-associated fibroblasts, induced by the exosomes derived from gastric cancer cells.
[Cell Death & Disease]
Gu, J., Li, X., Zhao, L., Yang, Y., Xue, C., Gao, Y., Li, J., Han, Q., Sun, Z., Bai, C., & Zhao, R. C. (2021). The role of PKM2 nuclear translocation in the constant activation of the NF-κB signaling pathway in cancer-associated fibroblasts. Cell Death & Disease, 12(4), 1–13. https://doi.org/10.1038/s41419-021-03579-x Cite
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Long Non-Coding RNA NORAD Promotes the Prostate Cancer Cell Extracellular Vesicle Release via microRNA-541-3p-Regulated PKM2 to Induce Bone Metastasis of Prostate Cancer

Researchers explored the molecular mechanism underlying the regulatory role of NORAD in bone metastasis of prostate cancer.
[Journal of Experimental & Clinical Cancer Research]
Hu, C., Chen, J., Qin, X., You, P., Ma, J., Zhang, J., Zhang, H., & Xu, J. (2021). Long non‐coding RNA NORAD promotes the prostate cancer cell extracellular vesicle release via microRNA-541-3p-regulated PKM2 to induce bone metastasis of prostate cancer. Journal of Experimental & Clinical Cancer Research, 40(1), 98. https://doi.org/10.1186/s13046-021-01891-0 Cite
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Smooth Muscle Cell–Specific PKM (Pyruvate Kinase M) 2 Promotes Smooth Muscle Cell Phenotypic Switching and Neointimal Hyperplasia

Investigators report that PKM2 deletion in SMC reduced injury-induced neointimal hyperplasia by inhibiting SMC proliferation and migration, suppressing synthetic phenotype, and reducing aerobic glycolysis associated with decreased extracellular signal-regulated kinase, mTOR, and signal transducer and activator of transcription 3 signaling.
[Arteriosclerosis, Thrombosis, and Vascular Biology]
Jain Manish, Dhanesha Nirav, Doddapattar Prakash, Nayak Manasa K., Guo Liang, Cornelissen Anne, Lentz Steven R., Finn Aloke V., & Chauhan Anil K. (n.d.). Smooth Muscle Cell–Specific PKM (Pyruvate Kinase M) 2 Promotes Smooth Muscle Cell Phenotypic Switching and Neointimal Hyperplasia. Arteriosclerosis, Thrombosis, and Vascular Biology, 0(0), ATVBAHA.121.316021. https://doi.org/10.1161/ATVBAHA.121.316021 Cite
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SUMOylation Disassembles the Tetrameric Pyruvate Kinase M2 to Block Myeloid Differentiation of Leukemia Cells

Scientists found that SUMOylation of the M2 isoform of pyruvate kinase, a rate-limiting glycolytic enzyme catalyzing the dephosphorylation of phosphoenolpyruvate to pyruvate, is prevalent in a variety of leukemic cell lines as well as primary samples from patients with leukemia through multiple-reaction monitoring based targeted mass spectrometry analysis.
[Cell Death & Disease]
Xia, L., Jiang, Y., Zhang, X.-H., Wang, X.-R., Wei, R., Qin, K., & Lu, Y. (2021). SUMOylation disassembles the tetrameric pyruvate kinase M2 to block myeloid differentiation of leukemia cells. Cell Death & Disease, 12(1), 1–13. https://doi.org/10.1038/s41419-021-03400-9 Cite
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SEMG1/2 Augment Energy Metabolism of Tumor Cells

By using a combination of the bioinformatics and various cellular and molecular assays, scientists demonstrated that SEMG1 and SEMG2 were frequently expressed in lung cancer clinical samples and cancer cell lines of different origins and were negatively associated with the survival rate of cancer patients.
[Cell Death & Disease]
Shuvalov, O., Kizenko, A., Petukhov, A., Fedorova, O., Daks, A., Bottrill, A., Snezhkina, A. V., Kudryavtseva, A. V., & Barlev, N. (2020). SEMG1/2 augment energy metabolism of tumor cells. Cell Death & Disease, 11(12), 1–14. https://doi.org/10.1038/s41419-020-03251-w Cite
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HDAC8-Dependent Deacetylation of PKM2 Directs Nuclear Localization and Glycolysis to Promote Proliferation in Hepatocellular Carcinoma

Investigators found that K62 residues were deacetylated, which was related to the prognosis of hepatocellular carcinoma. Further studies indicated that HDAC8 binds and deacetylates the K62 residue of PKM2.
[Cell Death & Disease]
Zhang, R., Shen, M., Wu, C., Chen, Y., Lu, J., Li, J., Zhao, L., Meng, H., Zhou, X., Huang, G., Zhao, X., & Liu, J. (2020). HDAC8-dependent deacetylation of PKM2 directs nuclear localization and glycolysis to promote proliferation in hepatocellular carcinoma. Cell Death & Disease, 11(12), 1–15. https://doi.org/10.1038/s41419-020-03212-3 Cite
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Cabozantinib-Based Combination Therapy for the Treatment of Hepatocellular Carcinoma

Human hepatocellular carcinoma (HCC) cell lines and HCC mouse models were used to assess the therapeutic efficacy and targeted molecular pathways of cabozantinib, either alone or in combination with the pan-mTOR inhibitor MLN0128 or the checkpoint inhibitor anti-PD-L1 antibody.
[Gut]
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Pyruvate Kinase M2 Mediates the Glycolysis in the Lymphatic Endothelial Cells and Its Potential Relation to the Progression of Lymphatic Malformations

The glycolysis index, including glucose uptake, ATP and lactate production stayed at a relatively high level in human dermal lymphatic endothelial cells (HDLECs) compared with HUVECS, while inhibition of PKM2 by shikinon or PKM2 knockdown could significantly suppress glycolysis, migration, tubular formation, and invasion of HDLECs.
[American Journal of Pathology]
Jiang, H., Zou, Y., Zhao, J., Li, X., Yang, S., Zhou, X., Mou, D., Zhong, W., & Cai, Y. (2020). Pyruvate kinase M2 mediates the glycolysis in the lymphatic endothelial cells and its potential relation to the progression of lymphatic malformations. The American Journal of Pathology, 0(0). https://doi.org/10.1016/j.ajpath.2020.10.003 Cite
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Modulation of PKM Activity affects the Differentiation of TH17 Cells

To understand how TEPP-46 and DASA-58 alter T cell function, scientists assessed their therapeutic activity in a mouse model of T cell–mediated autoimmunity that mimics multiple sclerosis.
[Science Signaling]
Seki, S. M., Posyniak, K., McCloud, R., Rosen, D. A., Fernández-Castañeda, A., Beiter, R. M., Serbulea, V., Nanziri, S. C., Hayes, N., Spivey, C., Gemta, L., Bullock, T. N. J., Hsu, K.-L., & Gaultier, A. (2020). Modulation of PKM activity affects the differentiation of TH17 cells. Science Signaling, 13(655). https://doi.org/10.1126/scisignal.aay9217 Cite
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APC Loss Induces Warburg Effect via Increased PKM2 Transcription in Colorectal Cancer

The effects of APC-loss or Wnt ligand on the identified enzymes, PKM2 and LDHA, as well as Warburg effects were investigated. A linkage between activation of Wnt/β-catenin signalling and cancer metabolism was analysed in tumour of Apcmin/+ mice and CRC patients. The roles of PKM2 in cancer metabolism, which depends on Wnt/β-catenin signalling, were assessed in xenograft-tumours.
[British Journal of Cancer]
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