Knockdown of PKM2 Enhances Radiosensitivity of Non-small cell Lung Cancer

Wang, Shijiang; Ma, Yan; Wang, Peiguo; Zheng, Shu; Liu, Bin; Sun, Xia; Zhang, Huaqi; Yu, Jinming

doi:10.1007/s12013-015-0567-y

Cited by 12 publications

(10 citation statements)

References 24 publications

(26 reference statements)

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“…The m6A demethylase-mediated demethylation of PKM2 mRNA promotes hepatocellular carcinoma tumorigenesis [ 52 ]. In addition, knockdown of PKM2 in lung cancer suppresses tumor growth and invasion [ 53 ] and enhances the efficacy of docetaxel [ 54 ] and radiosensitivity [ 55 ]. Pharmacologic activation of PKM2 by small molecules reduces lung tumor xenograft growth [ 56 ].…”

Section: Roles Of Pkm2 In Cancermentioning

confidence: 99%

Protein kinase function of pyruvate kinase M2 and cancer

Chen

2020

Cancer Cell Int

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Pyruvate kinase is a terminal enzyme in the glycolytic pathway, where it catalyzes the conversion of phosphoenolpyruvate to pyruvate and production of ATP via substrate level phosphorylation. PKM2 is one of four isoforms of pyruvate kinase and is widely expressed in many types of tumors and associated with tumorigenesis. In addition to pyruvate kinase activity involving the metabolic pathway, increasing evidence demonstrates that PKM2 exerts a non-metabolic function in cancers. PKM2 has been shown to be translocated into nucleus, where it serves as a protein kinase to phosphorylate various protein targets and contribute to multiple physiopathological processes. We discuss the nuclear localization of PKM2, its protein kinase function and association with cancers, and regulation of PKM2 activity.

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Section: Roles Of Pkm2 In Cancermentioning

confidence: 99%

Protein kinase function of pyruvate kinase M2 and cancer

Chen

2020

Cancer Cell Int

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“…12 Our data showed that PKM2 upregulation only partly reversed the effect of miR-1294 on DDPtreated cells, indicating that other targets of miR-1294, apart from PKM2 may contribute to miR-1294-mediated anti-tumor activity, such as IGF1R. Previous studies showed that silencing of PKM2 enhanced radiosensitivity of cervical cancer and non-small cell lung cancer, 28,39 suggesting that miR-1294/PKM2 axis may play a role in radiosensitivity of osteosarcoma.…”

Section: Dovepressmentioning

confidence: 62%

“…25 Cleavage of caspase 3 and PARP are two major fundamental proteins of programmed cell death. 28 MMP-2 and MMP-9 are related to tumor metastasis and are highly expressed in various malignant tumors. 29 In this study, the change of above-mentioned factors was in accordance with impaired cell proliferation, migration, and invasion, and increased cell apoptosis in miR-1294-upregulated…”

Section: Discussionmentioning

confidence: 99%

<p>Antitumor Effect of miR-1294/Pyruvate Kinase M2 Signaling Cascade in Osteosarcoma Cells</p>

Yuan¹,

Yu²,

Chen³

et al. 2020

OTT

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Background: MicroRNAs (miRNAs) can act as negative regulators of gene expression, and play a crucial role in cancer progression. The aim of this study was to investigate the role of miR-1294/pyruvate kinase M2 (PKM2) axis in osteosarcoma cells in vitro and in vivo. Methods: The function of miR-1294 and its association with PKM2 in osteosarcoma cells were studied by real-time PCR, CCK-8, Western blot, scratch test, transwell assay, flow cytometry, and dual-luciferase reporter assays. The effect of miR-1294 on tumor growth in vivo was evaluated in a subcutaneous xenograft model of osteosarcoma. Results: miR-1294 was downregulated in osteosarcoma cells. Forced overexpression of miR-1294 inhibited cell proliferation, migration, and invasion, and induced G0/G1 arrest and apoptosis. Consistently, protein expression levels of proliferating cell nuclear antigen, c-Myc, cyclin D1, active matrix metalloproteinase 2, and active matrix metalloproteinase 9 were decreased, and cleaved caspase 3 and cleaved PARP were increased following miR-1294 overexpression. Moreover, we demonstrated that PKM2 was a target of miR-1294 in osteosarcoma cells, and the effects caused by miR-1294 mimic were reversed by the overexpression of PKM2. Furthermore, we found that upregulation of miR-1294 inhibited tumorigenesis of osteosarcoma cells in vivo, which was accompanied by downregulation of PKM2. Conclusion: Our results revealed that miR-1294/PKM2 signaling cascade exerts important roles in the regulation of tumor progression, implying that this pathway may serve as a potential therapeutic target in osteosarcoma.

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“…PKM2 has been demonstrated to play a crucial function in tumorigenesis, 10,[12][13][14][15] cell cycling, angiogenesis, 16 invasion, [17][18][19] and radiosensitivity. [20][21][22][23] Although these findings point out that PKM2 plays an important role in the tumor progression, its specific role in remodeling tumor microenvironment and the underlying mechanisms are unclear. Interestingly, macrophage is one of the major cellular components in the tumor microenvironment and abundance of macrophages has been correlated with poor prognosis in human cancers, such as breast, prostate, ovarian, cervical, and lung carcinoma, 24 which attracts us to gain further insights into the relationship between PKM2 expression level and macrophage infiltration, and the molecular mechanisms through which PKM2 regulates macrophage recruitment in CRC microenvironment.…”

Section: Introductionmentioning

confidence: 99%

Specific tumor-derived CCL2 mediated by pyruvate kinase M2 in colorectal cancer cells contributes to macrophage recruitment in tumor microenvironment

Zou

Wang

et al. 2017

Tumour Biol.

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Development of colorectal cancer has been considered as a result of imbalance of pro-and anti-inflammatory intestinal microenvironment accompanied by macrophage recruitment. Despite macrophages are implicated in remodeling tumor microenvironment, the mechanism of macrophage recruitment is not fully elucidated yet. In this study, we reported clinical association of highly expressed pyruvate kinase M2 in colorectal cancer with macrophage attraction. The conditioned medium from Caco-2 and HT-29 cells with depleted pyruvate kinase M2 dramatically reduced macrophage recruitment, which is reversed by addition of, a critical chemotaxis factor to macrophage migration, rCCL2. Silencing of endogenous pyruvate kinase M2 markedly decreased CCL2 expression and secretion by real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Endogenous pyruvate kinase M2 interacted with p65 and mediated nuclear factor-κB signaling pathway and mainly regulated phosphorylation of Ser276 on p65 nuclear factor-κB. In addition, inhibition of macrophage recruitment caused by pyruvate kinase M2 silencing was rescued by ectopic expression of p65. Interestingly, pyruvate kinase M2 highly expressed in colorectal cancer tissue, which is correction with macrophage distribution. Taken together, we revealed a novel mechanism of pyruvate kinase M2 in promoting colorectal cancer progression by recruitment of macrophages through p65 nuclear factor-κB-mediated expression of CCL2.

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Knockdown of PKM2 Enhances Radiosensitivity of Non-small cell Lung Cancer

Cited by 12 publications

References 24 publications

Protein kinase function of pyruvate kinase M2 and cancer

Protein kinase function of pyruvate kinase M2 and cancer

<p>Antitumor Effect of miR-1294/Pyruvate Kinase M2 Signaling Cascade in Osteosarcoma Cells</p>

Specific tumor-derived CCL2 mediated by pyruvate kinase M2 in colorectal cancer cells contributes to macrophage recruitment in tumor microenvironment

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