Significance of semaphorin-3A and MMP-14 protein expression in non-small cell lung cancer

Zhou, Haiying; Wu, Xia; Fu, Wei; Lv, Zheng; Zhang, Zhiyong

doi:10.3892/ol.2014.1920

Cited by 40 publications

(29 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3D. Notably, these 24 genes were centred on GSK3β, FYN, MET, and SEMA3A, of which only SEMA3A is a known tumour suppresser, having been identified in many types of tumours, including lung cancer [31-34]. Our genome-wide screening data showed that knocking down SEMA3A was not synthetic lethal with p53 activation in A549 cells (Table S6).…”

Section: Resultsmentioning

confidence: 98%

Integrated High Throughput Analysis Identifies GSK3 as a Crucial Determinant of p53-Mediated Apoptosis in Lung Cancer Cells

Zhang¹,

Zhu²,

Sun³

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: p53 dysfunction is frequently observed in lung cancer. Although restoring the tumour suppressor function of p53 is recently approved as a putative strategy for combating cancers, the lack of understanding of the molecular mechanism underlying p53-mediated lung cancer suppression has limited the application of p53-based therapies in lung cancer. Methods and Results: Using RNA sequencing, we determined the transcriptional profile of human non-small cell lung carcinoma A549 cells after treatment with two p53-activating chemical compounds, nutlin and RITA, which could induce A549 cell cycle arrest and apoptosis, respectively. Bioinformatics analysis of genome-wide gene expression data showed that distinct transcription profiles were induced by nutlin and RITA and 66 pathways were differentially regulated by these two compounds. However, only two of these pathways, 'Adherens junction' and 'Axon guidance', were found to be synthetic lethal with p53 re-activation, as determined via integrated analysis of genome-wide gene expression profile and short hairpin RNA (shRNA) screening. Further functional protein association analysis of significantly regulated genes associated with these two synthetic lethal pathways indicated that GSK3 played a key role in p53-mediated A549 cell apoptosis, and then gene function study was performed, which revealed that GSK3 inhibition promoted p53-mediated A549 cell apoptosis in a p53 post-translational activity-dependent manner. Conclusion: Our findings provide us with new insights regarding the mechanism by which p53 mediates A549 apoptosis and may cast light on the development of more efficient p53-based strategies for treating lung cancer.

show abstract

Section: Resultsmentioning

confidence: 98%

Integrated High Throughput Analysis Identifies GSK3 as a Crucial Determinant of p53-Mediated Apoptosis in Lung Cancer Cells

Zhang¹,

Zhu²,

Sun³

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…SEMA3A expression is downregulated with the increasing degree of malignancy in human breast cancer SEMA3A expression is downregulated in various human cancers, including epithelial ovarian, breast, gastric, and non-small cell lung cancer compared with the respective normal tissue (20)(21)(22)(23). Immunohistochemical staining of 83 breast cancer patient samples with varying grades of malignancy (grade I and III ductal breast cancer accounted for 39 patient samples) revealed that SEMA3A expression is significantly downregulated in grade III ductal breast carcinoma compared with grade I (Fig.…”

Section: Resultsmentioning

confidence: 99%

Guidance Molecule SEMA3A Restricts Tumor Growth by Differentially Regulating the Proliferation of Tumor-Associated Macrophages

et al. 2016

View full text Add to dashboard Cite

Accumulation of tumor-associated macrophages (TAM) correlates with malignant progression, immune suppression, and poor prognosis. In this study, we defined a critical role for the cellsurface guidance molecule SEMA3A in differential proliferative control of TAMs. Tumor cell-derived SEMA3A restricted the proliferation of protumoral M2 macrophages but increased the proliferation of antitumoral M1, acting through the SEMA3A receptor neuropilin 1. Expansion of M1 macrophages in vivo enhanced the recruitment and activation of natural killer (NK) cells and cytotoxic CD8þ T cells to tumors, inhibiting their growth. In human breast cancer specimens, we found that immunohistochemical levels of SEMA3A correlated with the expression of genes characteristic of M1 macrophages, CD8 þ T cells, and NK cells, while inversely correlating with established characters of malignancy. In summary, our results illuminate a mechanism whereby the TAM phenotype is controlled and identify the cellsurface molecule SEMA3A as a candidate for therapeutic targeting.Cancer Res; 76(11); 3166-78. Ó2016 AACR.

show abstract

“…120 Sema3A also functions as a potent inhibitor of angiogenesis and tumor progression in many types of solid tumors. Down-regulation of sema3A expression in tumor cells promotes tumor angiogenesis and tumor progression in many types of solid tumors [121][122][123][124][125][125][126][127] suggesting that it functions as an endogenous negative regulator of the angiogenic switch. 128 Prolonged stimulation of endothelial cells with sema3A induces apoptosis of endothelial cells suggesting that induction of apoptosis is a part of the mechanism by which it inhibits angiogenesis.…”

Section: Semaphorins As Regulators Of Tumor Progressionmentioning

confidence: 99%

The role of the semaphorins in cancer

Neufeld

Mumblat

Smolkin

et al. 2016

Cell Adhesion & Migration

View full text Add to dashboard Cite

The semaphorins were initially characterized as axon guidance factors, but have subsequently been implicated also in the regulation of immune responses, angiogenesis, organ formation, and a variety of additional physiological and developmental functions. The semaphorin family contains more then 20 genes divided into 7 subfamilies, all of which contain the signature sema domain. The semaphorins transduce signals by binding to receptors belonging to the neuropilin or plexin families. Additional receptors which form complexes with these primary semaphorin receptors are also frequently involved in semaphorin signaling. Recent evidence suggests that semaphorins also fulfill important roles in the etiology of multiple forms of cancer. Some semaphorins have been found to function as bona-fide tumor suppressors and to inhibit tumor progression by various mechanisms while other semaphorins function as inducers and promoters of tumor progression. The semaphorin familyThe semaphorin family members are divided into 8 subclasses of which subclasses 1 and 2 contain invertebrate semaphorins while subclasses 3-7 contain the 22 vertebrate semaphorins. The 8th subclass contains viral semaphorins. In early publications, semaphorins were assigned confusing names. This situation was rectified by the adoption of a unified nomenclature in which sema is followed by the subclass number and by alphabetic designation within the subclass.1 Semaphorins are characterized by the presence of a »500 amino-acids long sema domain located close to their N-termini which is also present in semaphorin receptors of the plexin family, and by a plexin-semaphorin-integrin (PSI) domain located downstream to the sema domain. The sema domain is essential for semaphorin activity and plays a role in the determination of the receptor binding specificity.2 The sema domains of several different semaphorins were characterized by X-ray crystallography revealing a b propeller topology.3-5 Different semaphorin subclasses are characterized by class specific structural motifs. Thus, the vertebrate semaphorins belonging to classes 3, 4 and 7 contain immunoglobulin like domains, class-5 semaphorins contain thrombospondin repeats and class-3 semaphorins contain a basic domain. Class-3 semaphorins are the only vertebrate semaphorins produced as secreted proteins while other vertebrate semaphorins are membrane anchored or trans-membrane proteins that can be further processed into soluble forms by proteolytic cleavage (Fig.

show abstract

Significance of semaphorin-3A and MMP-14 protein expression in non-small cell lung cancer

Cited by 40 publications

References 23 publications

Integrated High Throughput Analysis Identifies GSK3 as a Crucial Determinant of p53-Mediated Apoptosis in Lung Cancer Cells

Integrated High Throughput Analysis Identifies GSK3 as a Crucial Determinant of p53-Mediated Apoptosis in Lung Cancer Cells

Guidance Molecule SEMA3A Restricts Tumor Growth by Differentially Regulating the Proliferation of Tumor-Associated Macrophages

The role of the semaphorins in cancer

Contact Info

Product

Resources

About