Upregulation of Cytoskeleton Protein and Extracellular Matrix Protein Induced by Stromal-Derived Nitric Oxide Promotes Lung Cancer Invasion and Metastasis

Zhang, L.; Liu, Jie; Wang, X.; Li, Z.; Zhang, X.; Cao, Pinjiang; She, Xiaoling; Dai, Qi-Shan; Tang, Jingling; Liu, Z.

doi:10.2174/1566524014666140724103147

Cited by 26 publications

(22 citation statements)

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“…Many factors are well known to be related to the metastatic or invasive potential of human cancer cells. For examples, nitric oxide promotes the invasive activity in lung cancer cells [36]; and changes energy metabolism (increased glycolysis), which affects the tumor-endothelial interaction of bladder carcinoma [37]. Recent evidence has suggested that calmodulin plays a crucial role in the modulation of cancer metastasis during gastric cancer [38].…”

Section: Discussionmentioning

confidence: 99%

Brain-derived neurotrophic factor (BDNF) -TrKB signaling modulates cancer-endothelial cells interaction and affects the outcomes of triple negative breast cancer

et al. 2017

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AimsThere is good evidence that the tumor microenvironment plays an important role in cancer metastasis and progression. Our previous studies have shown that brain-derived neurotrophic factor (BDNF) participates in the process of metastasis and in the migration of cancer cells. The aim of this study was to investigate the role of BDNF on the tumor cell microenvironment, namely, the cancer cell-endothelial cell interaction of TNBC cells.MethodsWe conducted oligoneucleotide microarray analysis of potential biomarkers that are able to differentiate recurrent TNBC from non-recurrent TNBC. The MDA-MB-231 and human endothelial HUVEC lines were used for this study and our approaches included functional studies, such as migration assay, as well as Western blot and real-time PCR analysis of migration and angiogenic signaling. In addition, we analyzed the survival outcome of TNBC breast cancer patients according to their expression level of BDNF using clinical samples.ResultsThe results demonstrated that BDNF was able to bring about autocrinal (MDA-MB-231) and paracrinal (HUVECs) regulation of BDNF-TrkB gene expression and this affected cell migratory activity. The BDNF-induced migratory activity was blocked by inhibitors of ERK, PI3K and TrkB when MDA-MB-231 cells were examined, but only an inhibitor of ERK blocked this activity when HUVEC cells were used. Furthermore, decreased migratory activity was found for △BDNF and △TrkB cell lines. Ingenuity pathway analysis (IPA) of MDA-MB-231 cells showed that BDNF is a key factor that is able to regulate a network made up of metalloproteases and calmodulin. Protein expression levels in a tissue array of tumor slices were found to be correlated with patient prognosis and the results showed that there was significant correlation of TrkB expression, but not of BDNF. expressionwith patient DFS and OS.ConclusionOur study demonstrates that up-regulation of the BDNF signaling pathway seems tobe involved in the mechanism associated with early recurrence in triple negative breast cancer cell. In addition, BDNF can function in either an autocrine or a paracrine manner to increase the migration ability of both MDA-MB-231 cells and HUVEC cells. Finally, overexpression of TrkB, but not of BDNF, is significantly associated with a poor survival outcome for TNBC patients.

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Section: Discussionmentioning

confidence: 99%

Brain-derived neurotrophic factor (BDNF) -TrKB signaling modulates cancer-endothelial cells interaction and affects the outcomes of triple negative breast cancer

et al. 2017

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“…iNOS derived NO have been associated with many tumors and in their progression into metastatsis. iNOS positivity has been reported consistently in human cancers at a variety of sites, including the lung [101] prostate [102] , breast [103] , bladder [104] , oral cavity, esophagus [105] and colon [106] . In each single case, the effects of NO have to be interpreted with regard to the microenvironment of the tumor.…”

Section: Tumor Inos and Nomentioning

confidence: 99%

“…iNOS may also serve as a biomarker for metastasis of lung cancer. In lung cancer patients with bone metastasis, the circulating metastatic cells were found to have increased iNOS expression contributing to increase in Epithelial Cell Adhesion Molecule (EpCAM) which is associated with metastasis due to reduced cell-cell-adhesion [101] .…”

Section: Tumor Inos and Nomentioning

confidence: 99%

The dual role of iNOS in cancer

2015

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Nitric oxide (NO) is one of the 10 smallest molecules found in nature. It is a simple gaseous free radical whose predominant functions is that of a messenger through cGMP. In mammals, NO is synthesized by the enzyme nitric oxide synthase (NOS) of which there are three isoforms. Neuronal (nNOS, NOS1) and endothelial (eNOS, NOS3) are constitutive calcium-dependent forms of the enzyme that regulate neural and vascular function respectively. The third isoform (iNOS, NOS2), is calcium-independent and is inducible. In many tumors, iNOS expression is high, however, the role of iNOS during tumor development is very complex and quite perplexing, with both promoting and inhibiting actions having been described. This review will aim to summarize the dual actions of iNOS-derived NO showing that the microenvironment of the tumor is a contributing factor to these observations and ultimately to cellular outcomes.

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“…nNOS and eNOS are constitutively present in peripheral nerves and vascular endothelial cells, respectively, whereas iNOS is inducible, mainly in pathological conditions, by mesenchymal cells and parenchymal cells through the stimulation of endotoxins and cytokines. The expression of NOS has been detected in various cancers such as breast, bladder, stomach, prostate, lung, colon, pancreas and renal cancers . In liver cancer, the expression pattern of NOS remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Nitric oxide inhibits autophagy and promotes apoptosis in hepatocellular carcinoma

et al. 2019

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Hepatocellular carcinoma (HCC) is the second most common cause of cancer‐related mortality worldwide. The expression of nitric oxide synthase (NOS) and the inhibition of autophagy have been linked to cancer cell death. However, the involvement of serum nitric oxide (NO), the expression of NOS and autophagy have not been investigated in HCC. In the present study, we first established that the NO level was significantly higher in hepatitis B virus‐related HCC than in the liver cirrhosis control (53.60 ± 19.74 vs 8.09 ± 4.17 μmol/L, t = 15.13, P < 0.0001). Using immunohistochemistry, we found that the source of NO was at least partially attributed to the expression of inducible NOS and endothelial NOS but not neuronal NOS in the liver tissue. Furthermore, in human liver cancer cells, NO‐induced apoptosis and inhibited autophagy. Pharmacological inhibition of autophagy also induced apoptosis, whereas the induction of autophagy could ameliorate NO‐induced apoptosis. We also found that NO regulates the switch between apoptosis and autophagy by disrupting the Beclin 1/Vps34 association and by increasing the Bcl‐2/Beclin 1 interaction. Overall, the present findings suggest that increased NOS/NO promotes apoptosis through the inhibition of autophagy in liver cancer cells, which may provide a novel strategy for the treatment of HCC.

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Upregulation of Cytoskeleton Protein and Extracellular Matrix Protein Induced by Stromal-Derived Nitric Oxide Promotes Lung Cancer Invasion and Metastasis

Cited by 26 publications

References 0 publications

Brain-derived neurotrophic factor (BDNF) -TrKB signaling modulates cancer-endothelial cells interaction and affects the outcomes of triple negative breast cancer

Brain-derived neurotrophic factor (BDNF) -TrKB signaling modulates cancer-endothelial cells interaction and affects the outcomes of triple negative breast cancer

The dual role of iNOS in cancer

Nitric oxide inhibits autophagy and promotes apoptosis in hepatocellular carcinoma

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