Effect of cancer-associated mutations in the PlexinB1 gene

Zhou, Chun; Wong, Oscar Gee‐Wan; Masters, J. R. W.; Williamson, Magali

doi:10.1186/1476-4598-11-11

Cited by 13 publications

(11 citation statements)

References 39 publications

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“…Engagement of integrins activate multiple signaling pathways that are associated with pro-tumorigenic activities, including invasion and metastasis [18, 19]. Our observation that DI17E6 suppressed activation of multiple integrin-activated signaling pathways suggests that inhibition of signaling could contribute to DI17E6’s anti-migration and invasive activity.…”

Section: Discussionmentioning

confidence: 92%

Abituzumab Targeting of αV-Class Integrins Inhibits Prostate Cancer Progression

Jiang

Dai

Yao

et al. 2017

Molecular Cancer Research

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Integrins that contain an integrin alpha V subunit contribute to multiple functions that promote cancer progression. The goal of this study was to determine if abituzumab (DI17E6, EMD 525797), a humanized monoclonal antibody (mAb) against integrin alpha V impacts, prostate cancer (PCa) progression. To evaluate this, PCa cells were treated with DI17E6 and its effects on proliferation, apoptosis, cell cycle, adhesion, detachment, migration, invasion and phosphorylation of downstream targets, including FAK, Akt and ERK were determined. DI17E6 promoted detachment and inhibited adhesion of PCa cells to several extracellular matrix (ECM) proteins and cells found in the bone microenvironment, but had no impact on cell viability, cell cycle and caspase 3/7 activity. DI17E6 inhibited migration and invasion of PCa cells. Additionally, DI7E6 decreased phosphorylation of FAK, Akt and ERK. These results indicate that inhibition of integrin alpha V with DI17E6 inhibits several pro-metastatic phenotypes of PCa cells and therefore provide a rationale for further evaluation of DI17E6 for diminishing PCa progression. Implications This work identifies that therapeutic targeting of integrins containing an alpha V integrin unit inhibits cancer progression and thus may be of clinical benefit.

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Section: Discussionmentioning

confidence: 92%

Abituzumab Targeting of αV-Class Integrins Inhibits Prostate Cancer Progression

Jiang

Dai

Yao

et al. 2017

Molecular Cancer Research

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“…22 Plexin-B1 interacts with ErbB2 in the prostate cancer cell line, LNCaP, and Sema4D induces the phosphorylation of ErbB2 in this cell line. Furthermore, knockdown of ErbB2 expression inhibits the Sema4D-induced motility of LNCaP cells, suggesting that activation of the Sema4D/plexin-B1 signalling pathway involving ErbB2 promotes the invasive behaviour of prostate cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Plexin-B1 signalling promotes androgen receptor translocation to the nucleus

2015

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Semaphorins and their receptors plexins have diverse roles in many cancers affecting tumour growth, metastasis and angiogenesis. Plexin-B1, the receptor for semaphorin4D (Sema4D), has been implicated in prostate cancer where mutation of the gene and overexpression of the protein occur. It is not clear, however, as to which of the several Sema4D-activated signalling pathways downstream of plexin-B1 function in prostate cancer progression. We show here that Sema4D/plexin-B1 increases the expression of androgen-responsive genes and activates the transcriptional activity of the androgen receptor (AR). Activation of plexin-B1 results in phosphorylation of AR at Serine 81, a site that is phosphorylated by nuclear kinases. Cell fractionation and immunocytochemistry studies demonstrated that the proportion of cells with AR in the nucleus increases significantly upon Sema4D treatment. The N-terminal (AF-1) domain of AR, which contains binding sites for transcription regulators, is not required for this response. Depletion of AR suppressed Sema4D-induced anchorage-independent growth of LNCaP and LNCaP-LN3 cells, demonstrating the functional significance of these findings. These results show that Sema4D/plexin-B1 signalling promotes the translocation of AR to the nucleus and thereby enhances AR transcriptional activity. Plexin-B1 is therefore a promising target for cancer therapy, especially in low androgen situations such as those imposed by androgen deprivation therapy.

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“…Plexin B1-mediated signalling pathways can be blocked by Plexin B1 mutations, which inhibit cell motility. Finally, Plexin B1 represents a new target candidate for drug action for treating ErbB2-positive breast cancer patients (Zhou et al 2012;Worzfeld et al 2012).…”

Section: Discussionmentioning

confidence: 99%

Genome-wide association study of antibody level response to NDV and IBV in Jinghai yellow chicken based on SLAF-seq technology

WenHao

Zhang

et al. 2015

J Appl Genetics

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Newcastle disease (ND) and avian infectious bronchitis (IB) are contagious diseases of chickens. To identify genes associated with antibody levels against ND and IB, a genome-wide association study was performed using specific-locus amplified fragment sequencing (SLAF-seq) technology in Jinghai yellow chickens. This determined six single-nucleotide polymorphisms (SNPs) that were associated with antibody levels against Newcastle disease virus (NDV): rsZ2494661, rsZ2494710, rs1211307701, rs1211307711, rs1218289310 and rs420701988. Of these, rsZ2494661 and rsZ2494710 reached the 5 % Bonferroni genome-wide significance level (5.5E-07) and they were both 134.7 kb downstream of the SETBP1 gene. The remaining four SNPs had 'suggestive' genome-wide significance levels (1.1E-05) and they were within or near the Plexin B1, LRRN1 and PDGFC genes. IB had two SNPs associated with antibody levels: rs149988433 and rs16170823; both reached chromosome-wide significance levels and they were near the USP7 and TRIM27 genes, respectively. Bioinformatics, GO annotation and pathway analysis indicated that five of these genes (Plexin B1, TRIM27, PDGFC, SETBP1 and USP7) may be important for the generation of protective antibodies against NDV and infectious bronchitis virus (IBV). This paves the way for further research on host immune responses against NDV.

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Effect of cancer-associated mutations in the PlexinB1 gene

Cited by 13 publications

References 39 publications

Abituzumab Targeting of αV-Class Integrins Inhibits Prostate Cancer Progression

Abituzumab Targeting of αV-Class Integrins Inhibits Prostate Cancer Progression

Plexin-B1 signalling promotes androgen receptor translocation to the nucleus

Genome-wide association study of antibody level response to NDV and IBV in Jinghai yellow chicken based on SLAF-seq technology

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