Pyruvate kinase M2 accelerates pro-inflammatory cytokine secretion and cell proliferation induced by lipopolysaccharide in colorectal cancer

Yang, Peng; Li, Zongwei; Li, Hanqing; Lu, Yangxu; Wu, Haili; Li, Zhuoyu

doi:10.1016/j.cellsig.2015.02.032

Cited by 69 publications

(48 citation statements)

References 40 publications

(54 reference statements)

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“…38 Similarly, Yang et al demonstrated that LPS could induce cell proliferation in colorectal cancer. 39 Consistently, Bedini et al found that LPS exerted a promoting effect on glioblastoma cell proliferation. 40 Moreover, LPS is also an important player in mediation of the epithelial-mesenchymal transition, a key process with enhanced migration and invasion during cancer progression.…”

Section: Discussionmentioning

confidence: 82%

Down-regulation of MRPS23 inhibits LPS-induced proliferation and invasionviaregulation of the NF-κB signaling pathway in osteosarcoma cells

Liu

Wang

et al. 2019

RSC Adv.

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Mitochondrial ribosomal protein S23 (MRPS23), encoded by a nuclear gene, is a participant in the translation of mitochondrial proteins. Recently, MRPS23 has been reported to be overexpressed in many types of cancers and have a close association with cancer progression. However, the specific roles of MRPS23 in osteosarcoma (OS) remain unknown. In this study, we investigated the expression pattern and biological functions of MRPS23 in OS cells. Our results demonstrated that MRPS23 was up-regulated in OS tissues and cell lines. Down-regulation of MRPS23 significantly inhibited OS cell proliferation and invasion induced by lipopolysaccharide (LPS) in vitro. Furthermore, the in vivo experiments showed that MRPS23 down-regulation markedly suppressed OS cell growth and metastasis induced by LPS. Mechanistically, down-regulation of MRPS23 inhibited the activity of NF-kB signaling pathway in OS cells. In conclusion, these findings indicated that MRPS23 may be a potential therapeutic target for OS treatment. Results Expression of MRPS23 is elevated in OS tissues and cell linesThe expression of MRPS23 in OS tissues was examined by immunohistochemistry, RT-PCR and western blot analysis. The

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Section: Discussionmentioning

confidence: 82%

Down-regulation of MRPS23 inhibits LPS-induced proliferation and invasionviaregulation of the NF-κB signaling pathway in osteosarcoma cells

Liu

Wang

et al. 2019

RSC Adv.

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“…The relationship between the p53 expression and PKM2 activity was further studied. We infected HeLa cells with lentivirus mediated PKM2 mutation vectors: K367M, K433E, R399E as described previously [21]. The results of pyruvate kinase activity showed that K367M and R399E mutants had much lower pyruvate kinase activity than that of their wild-type counterpart.…”

Section: Resultsmentioning

confidence: 99%

Overexpression of PKM2 promotes mitochondrial fusion through attenuated p53 stability

Yang

et al. 2016

Oncotarget

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M2-type pyruvate kinase (PKM2) contributes to the Warburg effect. However, it remains unknown as to whether PKM2 has an inhibitory effect on mitochondrial function. We report in this work that PKM2 overexpression inhibits the expression of Drp1 and results in the mitochondrial fusion. The ATP production was found to be decreased, the mtDNA copy number elevated and the expression level of electron transport chain (ETC) complex I, III, V depressed in PKM2 overexpressed cells. PKM2 overexpression showed a decreased p53 protein level and a shorter p53 half-life. In contrast, PKM2 knockdown resulted in increased p53 expression and prolonged half-life of p53. PKM2 could directly bind with both p53 and MDM2 and promote MDM2-mediated p53 ubiquitination. The dimeric PKM2 significantly suppressed p53 expression compared with the other PKM2 mutants. The reverse relationship between PKM2 and Drp1 was further confirmed in a large number of clinical samples. Taken together, the present results highlight a new mechanism that link PKM2 to mitochondrial function, based on p53-Drp1 axis down regulation, revealing a novel therapeutic target in patients with abnormal mitochondria.

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“…Aberrant expression of S100A8 has been found in different types of tumors including CRC (9) and the accumulation of S100A8 positive cells is always located in the invasive margin of colorectal carcinoma (10) which plays a critical role in the tumor microenvironment. Interestingly, mounting evidence indicates that the apical surface of the intestinal epithelium is exposed to lipopolysaccharides (LPS) from the lumen due to intestinal mucosal permeability and bacterial translocation (11). LPS could cause a cascade of inflammatory responses mediated by diverse inflammatory cells that secrete various chemokines and cytokines favoring CRC growth and migration.…”

Section: Introductionmentioning

confidence: 99%

S100A8 facilitates the migration of colorectal cancer cells through regulating macrophages in the inflammatory microenvironment

Zha

Sun

et al. 2016

Oncology Reports

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Abstract.Previous studies have shown that S100 calcium-binding protein A8 (S100A8) contributes to the survival and migration of colorectal cancer (CRC) cells. However, whether S100A8 participates in the progression and metastasis of CRC via the regulation of macrophages in the tumor inflammatory microenvironment remains unknown. In this study, phorbol myristate acetate (PMA) was used to induce the differentiation of THP-1 monocytes to macrophages. MTT assay, western blot analysis, immunofluorescence staining, semi-quantitative RT-PCR (semi-PCR), quantitative real-time PCR (qPCR), Gaussia luciferase activity assay and ELISA were performed to analyze the roles and molecular mechanisms of S100A8 in the modulation of macrophages. MTT assay, flow cytometric analysis, Hoechst staining, wound healing and Transwell migration assay were used to test the effect of S100A8 on the viability and migration of CRC cells co-cultured with macrophages in the inflammatory microenvironment. We found that THP-1 monocytes were induced by PMA and differentiated to macrophages. S100A8 activated the NF-κB pathway in the macrophages and promoted the expression of miR-155 and inflammatory cytokines IL-1β and TNF-α in the inflammatory microenvironment mimicked by lipopolysaccharides (LPS). Furthermore, S100A8 contributed to augment the migration but not the viability of the CRC cells co-cultured with the macrophages in the inflammatory microenvironment. Altogether, our study demonstrated that S100A8 facilitated the migration of CRC cells in the inflammatory microenvironment, and the underlying molecular mechanisms may be partially attributed to the overexpression of miR-155, IL-1β and TNF-α through activation of the NF-κB pathway in macrophages. IntroductionColorectal cancer (CRC), for which distant metastasis accounts for the leading cause of cancer mortality, is one of the most malignant gastrointestinal carcinomas worldwide (1). The pathogenesis of CRC is a complex process and involves environmental influences, genetic alterations, and the host immune system and their interactions. The formation of an inflammatory microenvironment also plays a pivotal role in the development of CRC (2). The host microenvironment is comprised of numerous infiltrating immune cell types and resident tumor cells. Among the immune cells, macrophages play an indispensable role. For instance, macrophage infiltration in colon tissue has been observed in both inflammatory bowel disease (IBD) and CRC (4), and the cytokines secreted by macrophages under certain conditions have directly or indirectly stimulated inflammation and tumor progression (5,6). Although great progress has been made, the interactions and the molecular mechanisms between CRC and the inflammatory microenvironment remain unknown. S100A8 (calgranulin A or S100 calcium-binding protein A8) is a member of the low-molecular calcium binding S100 protein family. It also belongs to the family of damage-associated molecular patterns (DAMPs). Studies have shown that S100A8 plays an important role in regul...

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Pyruvate kinase M2 accelerates pro-inflammatory cytokine secretion and cell proliferation induced by lipopolysaccharide in colorectal cancer

Cited by 69 publications

References 40 publications

Down-regulation of MRPS23 inhibits LPS-induced proliferation and invasionviaregulation of the NF-κB signaling pathway in osteosarcoma cells

Down-regulation of MRPS23 inhibits LPS-induced proliferation and invasionviaregulation of the NF-κB signaling pathway in osteosarcoma cells

Overexpression of PKM2 promotes mitochondrial fusion through attenuated p53 stability

S100A8 facilitates the migration of colorectal cancer cells through regulating macrophages in the inflammatory microenvironment

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