EGFR and IGF‐1R in regulation of prostate cancer cell phenotype and polarity: opposing functions and modulation by T‐cadherin

Maslova, Kseniya; Kyriakakis, Emmanouil; Pfaff, Dennis; Frachet, Audrey; Frismantiene, Agne; Bubendorf, Lukas; Ruiz, Christian; Vlajnic, Tatjana; Erné, Paul; Resink, Thérèse J.; Philippova, Maria

doi:10.1096/fj.14-249367

Cited by 17 publications

(13 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In support of this hypothesis is the evidence that Tcadherin controls PCa cell epithelial polarity via regulation of EGFR and IGF-1R activities which are important for prostate differentiation and tumour growth [49].…”

Section: Discussionmentioning

confidence: 85%

“…Together, these data suggest that changes in T‐cadherin expression in PCa are associated with deregulated differentiation of prostate epithelial cells. In support of this hypothesis is the evidence that T‐cadherin controls PCa cell epithelial polarity via regulation of EGFR and IGF‐1R activities which are important for prostate differentiation and tumour growth .…”

Section: Discussionmentioning

confidence: 87%

“…We found that T‐cadherin impacts PCa cell sensitivity to doxorubicin, an antibiotic of the anthracycline family which is widely used as a chemotherapy agent to treat many types of neoplasia including PCa. PCa cell line DU145 used in the study derives from brain metastasis, exhibits significant resistance to doxorubicin and does not express T‐cadherin . Ectopic expression of T‐cadherin sensitises DU145 cells to doxorubicin reducing cell viability.…”

Section: Discussionmentioning

confidence: 99%

“…T-cadherin was identified as an androgen-responsive gene and reported to inhibit PCa cell proliferation and anchorage-independent growth [48]. Our own recent investigation unexpectedly found that T-cadherin overexpression promoted migration and invasion of benign prostate cell line BPH-1 and metastatic cell line DU145 [49]. These functional phenomena were accompanied by loss of epithelial morphology and were likely due to a change in activities of epidermal growth factor receptor (EGFR) and insulin-like growth factor-1 receptor (IGF-1R).…”

Section: Introductionmentioning

confidence: 96%

See 3 more Smart Citations

T‐cadherin in prostate cancer: relationship with cancer progression, differentiation and drug resistance

Dasen

Vlajnic

Mengus

et al. 2016

The Journal of Pathology CR

Self Cite

View full text Add to dashboard Cite

Prostate cancer represents the second leading cause of cancer‐related death in men. T‐cadherin (CDH13) is an atypical GPI‐anchored member of the cadherin family of adhesion molecules. Its gene was reported to be downregulated in a small series of prostate tumours. T‐cadherin protein expression/localisation in prostate tissue has never been investigated. The purpose of our study was to analyse CDH13 gene and protein levels in large sets of healthy and cancer prostate tissue specimens and evaluate CDH13 effects on the sensitivity of prostate cancer cells to chemotherapy. Analysis of CDH13 gene expression in the TCGA RNAseq dataset for prostate adenocarcinoma (N = 550) and in tissue samples (N = 101) by qPCR revealed weak positive correlation with the Gleason score in cancer and no difference between benign and malignant specimens. Immunohistochemical analysis of tissue sections (N = 12) and microarrays (N = 128 specimens) demonstrated the presence of CDH13 on the apical surface and at intercellular contacts of cytokeratin 8‐positive luminal cells and cells double‐positive for cytokeratin 8 and basal marker p63. T‐cadherin protein expression was markedly upregulated in cancer as compared to benign prostate hyperplasia, the increase being more prominent in organ‐confined than in advanced hormone‐resistant tumours, and correlated negatively with the Gleason pattern. T‐cadherin protein level correlated strongly with cytokeratin 8 and with an abnormal diffuse/membrane localisation pattern of p63. Ectopic expression of CDH13 in metastatic prostate cancer cell line DU145 reduced cell growth in the presence of doxorubicin. We conclude that CDH13 protein, but not its gene expression, is strongly upregulated in early prostate cancer, correlates with changes in luminal/basal differentiation and p63 localisation, and promotes sensitivity of cancer cells to doxorubicin. These data identify CDH13 as a novel molecule relevant for prostate cancer progression and response to therapy.

show abstract

Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

See 2 more Smart Citations

T‐cadherin in prostate cancer: relationship with cancer progression, differentiation and drug resistance

Dasen

Vlajnic

Mengus

et al. 2016

The Journal of Pathology CR

Self Cite

View full text Add to dashboard Cite

show abstract

“…EGF may cause elevations in E-cadherin, which may promote the phosphorylation of epidermal growth factor receptor (EGFR) and cell proliferation signals [8]. Recent studies have shown that the inhibition of EGFR was linked to decreased proliferation signals to prostatic epithelial cell lines [9]. …”

Section: Introductionmentioning

confidence: 99%

Association Study of Polymorphisms of Epidermal Growth Factor and Epidermal Growth Factor Receptor With Benign Prostatic Hyperplasia in a Korean Population

et al. 2016

View full text Add to dashboard Cite

PurposeRecent studies have suggested that specific single-nucleotide polymorphisms (SNPs) contribute to the clinical features of benign prostatic hyperplasia (BPH). In this study, we investigated the relationships of genetic polymorphisms of the epidermal growth factor (EGF) gene and the epidermal growth factor receptor (EGFR) gene with BPH.MethodsA total of 218 patients with BPH were enrolled in this study. We evaluated the relationship between eight SNPs in the EGF and EGFR genes and prostate volume, prostate-specific antigen (PSA), and International Prostate Symptom Score of BPH patients. Each SNP was genotyped by direct sequencing. Statistical analysis applying codominant, dominant, recessive, and log-additive models was performed via logistic regression.ResultsThe rs11568943 and rs11569017 SNPs in the EGF gene showed significant associations with prostate volume (rs11568943: P=0.038 in the log-additive model, P=0.024 in the allele distribution; rs11569017, P=0.031 in the dominant model, P=0.028 in the log-additive model, P=0.020 in the allele distribution). Additionally, the rs3756261, rs11568943, and rs11569017 SNPs of the EGF gene and the rs2293347 SNP of the EGFR gene were associated with PSA levels (P<0.05 in each model, respectively).ConclusionsThese results suggest that the EGF gene may affect prostate volume. In addition, the EGF and EGFR genes may be associated with PSA levels in patients with BPH.

show abstract

Matrix metalloproteinase‐1 facilitates MSC migration via cleavage of IGF‐2/IGFBP2 complex

et al. 2017

View full text Add to dashboard Cite

The specific mechanism underlying the tumor tropism of human mesenchymal stem cells (MSCs) for cancer is not well defined. We previously showed that the migration potential of MSCs correlated with the expression and protease activity of matrix metalloproteinase (MMP)‐1. Furthermore, highly tumor‐tropic MSCs expressed higher levels of MMP‐1 and insulin‐like growth factor (IGF)‐2 than poorly migrating MSCs. In this study, we examined the functional roles of IGF‐2 and MMP‐1 in mediating the tumor tropism of MSCs. Exogenous addition of either recombinant IGF‐2 or MMP‐1 could stimulate MSC migration. The correlation between IGF‐2, MMP‐1 expression, and MSC migration suggests that MMP‐1 may play a role in regulating MSC migration via the IGF‐2 signaling cascade. High concentrations of IGF binding proteins (IGFBPs) can inhibit IGF‐stimulated functions by blocking its binding to its receptors and proteolysis of IGFBP is an important mechanism for the regulation of IGF signaling. We thus hypothesized that MMP‐1 acts as an IGFBP2 proteinase, resulting in the cleavage of IGF‐2/IGFBP2 complex and extracellular release of free IGF‐2. Indeed, our results showed that conditioned media from highly migrating MSCs, which expressed high levels of MMP‐1, cleaved the IGF‐2/IGFBP2 complex. Taken together, these results showed that the MMP‐1 secreted by highly tumor‐tropic MSCs cleaved IGF‐2/IGFBP2 complex. Free IGF‐2 released from the complex may facilitate MSC migration toward tumor.

show abstract

EGFR and IGF‐1R in regulation of prostate cancer cell phenotype and polarity: opposing functions and modulation by T‐cadherin

Cited by 17 publications

References 50 publications

T‐cadherin in prostate cancer: relationship with cancer progression, differentiation and drug resistance

T‐cadherin in prostate cancer: relationship with cancer progression, differentiation and drug resistance

Association Study of Polymorphisms of Epidermal Growth Factor and Epidermal Growth Factor Receptor With Benign Prostatic Hyperplasia in a Korean Population

Matrix metalloproteinase‐1 facilitates MSC migration via cleavage of IGF‐2/IGFBP2 complex

Contact Info

Product

Resources

About