Myeloid cell RelA/p65 promotes lung cancer proliferation through Wnt/β-catenin signaling in murine and human tumor cells

Li, D; Beißwenger, Christoph; Herr, Christian; Hellberg, Jan; Han, Gang; Zakharkina, Tetyana; Voss, Meike; Wiewrodt, Rainer; Bohle, Rainer M.; Menger, Michael D.; Schmid, Roland M.; Stöckel, Daniel; Hp, Lenhof; Bals, Robert

doi:10.1038/onc.2013.75

Cited by 54 publications

(62 citation statements)

References 50 publications

(62 reference statements)

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“…The number of CRAMPpositive myeloid cells was significantly decreased in the tumor tissue of rela D À / À mice, while the total number of myeloid cells in the tumor tissue was unchanged. 27 The NF-kB signaling pathway has an important role in the regulation of cathelicidin. Inhibition of NF-kB by small interfering RNA and overexpression of IkBa reduced both basal and induced levels of Camp mRNA in murine mast cells.…”

Section: Discussionmentioning

confidence: 99%

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Expression of the antimicrobial peptide cathelicidin in myeloid cells is required for lung tumor growth

Beißwenger

Herr

et al. 2013

Oncogene

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Antimicrobial peptides, such as the cathelicidin LL-37/hCAP-18 and its mouse homolog cathelicidin-related antimicrobial peptide (CRAMP), are important effectors of the innate immune system with direct anti-bacterial activity. Cathelicidin is possibly involved in the regulation of tumor cell growth. The aim of this study was to characterize the role of cathelicidin expressed in non-tumorous cells in a preclinical mouse model of tumor growth. Wild-type and CRAMP-deficient animals were exposed to cigarette smoke (CS) and Lewis lung carcinoma cells were injected to initiate the growth of tumors in the lung. CS exposure significantly increased the proliferation of lung tumors in wild-type mice, but not in CRAMP-deficient mice. CS exposure induced the recruitment of myeloid cell into tumor tissue in a CRAMP-dependent manner. Mice lacking RelA/p65 specifically in myeloid cells showed impaired recruitment of CRAMP-positive cells into the lung. In vitro studies with human cells showed that LL-37/hCAP-18 in macrophages is induced by soluble factors derived from cancer cells. Taken together, these data indicate that cathelicidin expressed from myeloid cells promotes CS-induced lung tumor growth by further recruitment of inflammatory cells. The regulation of cathelicidin expression involves myeloid p65/RelA and soluble factor from tumor cells.

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Section: Discussionmentioning

confidence: 99%

“…As shown earlier, the influx of macrophages and neutrophils in smoke-exposed lungs depends on myeloid p65/RelA. 27 We compared the relative CRAMP mRNA expression in the lungs of air and CS-exposed mice.…”

Section: Introductionmentioning

confidence: 99%

Expression of the antimicrobial peptide cathelicidin in myeloid cells is required for lung tumor growth

Beißwenger

Herr

et al. 2013

Oncogene

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“…Studies showed that CS-induced and tumorassociated inflammation in the tumor microenvironment promote LC growth via the release of inflammatory mediators by inflammatory cells (12,14,15,31). We and the Karin group showed that the nuclear factor-B (NF-B) pathway in myeloid cells is a key regulator of CS-promoted LC development in metastatic LC and K-ras-induced mouse models.…”

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confidence: 97%

“…Preclinical and clinical studies suggest that there is a causal relation between inflammation and LC development (12,14,15,22,31,33). Studies showed that CS-induced and tumorassociated inflammation in the tumor microenvironment promote LC growth via the release of inflammatory mediators by inflammatory cells (12,14,15,31).…”

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confidence: 98%

Cigarette smoke-induced disruption of pulmonary barrier and bacterial translocation drive tumor-associated inflammation and growth

Jungnickel

Wonnenberg

Karabiber

et al. 2015

American Journal of Physiology-Lung Cellular and Molecular Phys

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Microorganisms have an important role in tumorgenesis by the induction of inflammation and by a direct impact on tumor cells. Chronic obstructive pulmonary disease (COPD) is associated with an increased risk for lung cancer and microbial colonization. We asked whether bacterial pathogens act as tumor promoters during CS-induced pulmonary inflammation. In a metastatic lung cancer (LC) model, Lewis lung carcinoma (LLC) cells were injected in mice to initiate the growth of tumors in the lung. Exposure to the combination of cigarette smoke (CS) and nontypeable Haemophilus influenzae (NTHi) synergistically increased metastatic growth. Lung levels of albumin and LDH, translocation of bacterial factors into tumor tissue, tumor inflammation, and tumor proliferation were significantly increased in mice exposed to CS in combination with NTHi. Bacterial pathogens increased the proliferation of cultured LLC cells and human cancer cell lines. Metastatic growth induced by the exposure to CS in combination with NTHi was reduced in mice deficient for IL-17. Our data provide evidence that CS-induced loss of pulmonary barrier integrity allows bacterial factors to translocate into tumor tissue and to regulate tumor-associated inflammation and tumor proliferation. Translocation of bacterial factors in tumor tissue links CS-induced inflammation with tumor proliferation.

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“…In addition, GSK3β was a phosphorylation substrate of Akt 17. Activation of Akt promoted the phosphorylation of GSK3β at Ser9, which in turn inhibited the degradation of β‐catenin and activated Wnt/β‐catenin signaling pathway 31. In this study, we found that IQUB overexpression increased the expression of p‐Akt, p‐GSK3β, and inhibited p‐β‐catenin, whereas IQUB knockdown showed the opposite effect.…”

Section: Discussionmentioning

confidence: 52%

Upregulated IQUB promotes cell proliferation and migration via activating Akt/GSK3β/β‐catenin signaling pathway in breast cancer

Zhang

et al. 2018

Cancer Medicine

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Breast cancer was the highest incidence of tumor in women, which seriously threaten women's health. Our previous study found that the expression of IQUB (IQ motif and ubiquitin domain containing) was significantly increased in the development of breast cancer by transcriptome sequencing. However, there were no studies on the mechanism of IQUB in tumorigenesis. Further study showed that IQUB expression was significantly increased in breast cancer, which had a significantly positive correlation with pathological differentiation of breast cancer by tissue microarray analysis. Furthermore, we also discovered that IQUB overexpression could obviously promote the proliferation and migration of MCF‐7 cells and increase the proportion of MCF‐7 cells in S and G2/M phase in vitro study, while knockdown of IQUB caused inhibition of cell proliferation and migration in MDA‐MB‐231 cells and increased the proportion of MDA‐MB‐231 cells in G1 phase. Furthermore, IQUB overexpression or knockdown combined with treatment of Licl or MG‐132 showed that IQUB activated Akt to promote GSK3β phosphorylation, which in turn activated Wnt/β‐catenin signaling pathway in breast cancer cells. Taken together, these results indicated that upregulated IQUB promoted breast cancer cell proliferation and migration via activating Akt/GSK3β/β‐catenin signaling pathway, which played an important part in the tumorigenesis and development of breast cancer.

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Myeloid cell RelA/p65 promotes lung cancer proliferation through Wnt/β-catenin signaling in murine and human tumor cells

Cited by 54 publications

References 50 publications

Expression of the antimicrobial peptide cathelicidin in myeloid cells is required for lung tumor growth

Expression of the antimicrobial peptide cathelicidin in myeloid cells is required for lung tumor growth

Cigarette smoke-induced disruption of pulmonary barrier and bacterial translocation drive tumor-associated inflammation and growth

Upregulated IQUB promotes cell proliferation and migration via activating Akt/GSK3β/β‐catenin signaling pathway in breast cancer

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