Function of mutant and wild‐type plexinB1 in prostate cancer cells

Damola, Adebiyi; Legendre, Anne; Ball, Stephen G.; Masters, J. R. W.; Williamson, Magali

doi:10.1002/pros.22678

Cited by 19 publications

(18 citation statements)

References 35 publications

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“…LNCaP-LN3, a derivative of the prostate cancer cell line LNCaP, has lost the mutant allele of plexin-B1 found in LNCaP, and it expresses wild-type (WT) plexin-B1 only. 23 LNCaP and LNCaP-LN3 cells were serum starved and then treated with Sema4D (2 μg/ml) for 48hrs or with PBS or dihydrotestosterone (DHT, 1 nM) as controls. Expression of KLK3 increased significantly in both cell lines following treatment with Sema4D ( Figure 1a).…”

Section: Sema4d Affects the Expression Of Androgen-responsive Genesmentioning

confidence: 99%

“…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. 23 ErbB2 overexpression occurs in late-stage prostate cancer, as do mutations in plexin-B1. Sema4D/plexin-B1 signalling may therefore increase the invasive characteristics of prostate cancer cells via activation of ErbB2 and Rho and via mutation of plexin-B1 in late-stage prostate cancer, in a similar way to breast cancer.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Sema4d Affects the Expression Of Androgen-responsive Genesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Plexin-B1 signalling promotes androgen receptor translocation to the nucleus

2015

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“…232 Regardless of the mechanisms involved, there are numerous observations suggesting that sema4D plays a stimulatory role in the progression of several types of tumors including head and neck tumors, breast carcinomas, ovarian cancinomas, pancreatic carcinoma, prostate cancer and soft tissue sarcomas such as osteosarcoma. [233][234][235][236][237][238][239] These observations lead to the development of inhibitory humanized antibodies that are developed as anti-tumorigenic drugs that target sema4D. 240 However, there are also opposite observations.…”

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confidence: 99%

“…36 Similar observations were also reported in prostate cancer cells. 238 It was recently also observed that the activation of plexin-B1 by Sema4D in breast carcinoma cells results in tyrosine phosphorylation of plexin-B1 by Met, thus creating a docking site for the SH2 domain of growth factor receptor bound-2 (Grb2). Grb2 is thereby recruited into the plexin-B1 receptor complex and through its SH3 domain, interacts with p190 RhoGAP and mediates RhoA deactivation and leads to the subsequent inhibition of breast carcinoma cells motility.…”

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confidence: 99%

The role of the semaphorins in cancer

Neufeld

Mumblat

Smolkin

et al. 2016

Cell Adhesion & Migration

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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.

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“…Damola et al (2013) reported that the invasive phenotype of prostate cancer cells could be increased by Plexin B1 signals via ErbB2. Plexin B1-mediated signalling pathways can be blocked by Plexin B1 mutations, which inhibit cell motility.…”

Section: Discussionmentioning

confidence: 98%

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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Function of mutant and wild‐type plexinB1 in prostate cancer cells

Cited by 19 publications

References 35 publications

Plexin-B1 signalling promotes androgen receptor translocation to the nucleus

Plexin-B1 signalling promotes androgen receptor translocation to the nucleus

The role of the semaphorins in cancer

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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