Aromatase-induced endogenous estrogen promotes tumour metastasis through estrogen receptor-α/matrix metalloproteinase 12 axis activation in castration-resistant prostate cancer

Liang, Zhixian; Cao, Jiasong; Tian, Lei; Shen, Yongmei; Lin, Qimei; Zhang, Ran; Liu, Haitao; Du, Xiaoling; Shi, Jiandang; Zhang, Ju

doi:10.1016/j.canlet.2019.09.001

Cited by 21 publications

(25 citation statements)

References 63 publications

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“…These cancer cells exhibit high expression of aromatase, leading to increased estrogen secretion. Estrogen, through ERα, enhances matrix metalloproteinase 12 (MMP12), ECM remodeling, and correlated PC invasion [ 116 ]. Therefore, enhanced secretion of endogenous estrogen, produced by increased aromatase levels, promoted the ERα-dependent expression of MMP12 expression, resulting in ECM remodeling in this PC model.…”

Section: Role Of Pgs In Hormone-dependent Cancer Growth Metastasimentioning

confidence: 99%

Proteoglycans in the Pathogenesis of Hormone-Dependent Cancers: Mediators and Effectors

Tzanakakis

Giatagana

Kuskov

et al. 2020

Cancers

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Hormone-dependent cancers exhibit high morbidity and mortality. In spite of advances in therapy, the treatment of hormone-dependent cancers remains an unmet health need. The tumor microenvironment (TME) exhibits unique characteristics that differ among various tumor types. It is composed of cancerous, non-cancerous, stromal, and immune cells that are surrounded and supported by components of the extracellular matrix (ECM). Therefore, the interactions among cancer cells, stromal cells, and components of the ECM determine cancer progression and response to therapy. Proteoglycans (PGs), hybrid molecules consisting of a protein core to which sulfated glycosaminoglycan chains are bound, are significant components of the ECM that are implicated in all phases of tumorigenesis. These molecules, secreted by both the stroma and cancer cells, are crucial signaling mediators that modulate the vital cellular pathways implicated in gene expression, phenotypic versatility, and response to therapy in specific tumor types. A plethora of deregulated signaling pathways contributes to the growth, dissemination, and angiogenesis of hormone-dependent cancers. Specific inputs from the endocrine and immune systems are some of the characteristics of hormone-dependent cancer pathogenesis. Importantly, the mechanisms involved in various aspects of cancer progression are executed in the ECM niche of the TME, and the PG components crucially mediate these processes. Here, we comprehensively discuss the mechanisms through which PGs affect the multifaceted aspects of hormone-dependent cancer development and progression, including cancer metastasis, angiogenesis, immunobiology, autophagy, and response to therapy.

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Section: Role Of Pgs In Hormone-dependent Cancer Growth Metastasimentioning

confidence: 99%

Proteoglycans in the Pathogenesis of Hormone-Dependent Cancers: Mediators and Effectors

Tzanakakis

Giatagana

Kuskov

et al. 2020

Cancers

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“…The progressive emergence of the ERα and ERα-regulated genes (e.g., progesterone receptor, PS2, TMPRSS2-ERG fusion and NEAT1) during PCa progression and hormone refractory disease suggests that these tumors can bypass the AR by using estrogens and progestins for their growth. Indeed, in CRPC Cyp19a1 expression was significantly increased in tumor samples [55]. In PCa cell lines, the androgen receptor antagonist BCT increased Cyp19a1 expression and ERβ transcriptional activity.…”

Section: Discussionmentioning

confidence: 96%

Phosphodiesterase Type-5 Inhibitor Tadalafil Modulates Steroid Hormones Signaling in a Prostate Cancer Cell Line

Bimonte

Marampon

Antonioni

et al. 2021

IJMS

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Background: The androgen receptor (AR) plays a key role in normal prostate homeostasis and in prostate cancer (PCa) development, while the role of aromatase (Cyp19a1) is still unclear. We evaluated the effects of a treatment with Tadalafil (TAD) on both these proteins. Methods: Androgen-sensitive human PCa cell line (LnCAP) was incubated with/without TAD (10−6 M) and bicalutamide (BCT) (10−4 M) to evaluate a potential modulation on cell proliferation, protein and mRNA expression of Cyp19a, AR and estrogen receptor-β (ERβ), respectively. Results: TAD increased early AR nuclear translocation (p < 0.05, after 15 min of exposure), and increased AR transcriptional activity (p < 0.05) and protein expression (p < 0.05) after 24 h. Moreover, after 24 h this treatment upregulated Cyp19a1 and ERβ mRNA (p < 0.05 and p < 0.005 respectively) and led to an increase in protein expression of both after 48 h (p < 0.05). Interestingly, TAD counteracted Cyp19a1 stimulation induced by BCT (p < 0.05) but did not alter the effect induced by BCT on the AR protein expression. Conclusion: We demonstrate for the first time that TAD can significantly modulate AR expression and activity, Cyp19a1 and ERβ expression in PCa cells, suggesting a specific effect of these proteins. In addition, TAD potentiates the antiproliferative activity of BCT, opening a new clinical scenario in the treatment of PCa.

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“…The level of CYP19A1 expression was also correlated with the Gleason score in primary PCa patients [11].…”

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confidence: 94%

The CYP19A1 (TTTA)n repeat polymorphism, but not Arg264Cys polymorphism, may affect the risk of prostate cancer: evidence from a meta-analysis

Guo

Liu

et al. 2021

Preprint

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Background: Abnormal aromatase (CYP19A1) expression may participate in prostate cancer (PCa) carcinogenesis. However, results of studies on the CYP19A1 gene polymorphisms and PCa are conflicting.This meta-analysis aimed to systematically evaluate the association between the CYP19A1 Arg264Cys polymorphism and (TTTA)n repeat polymorphism and PCa.Methods: Electronic databases (PubMed, EmBase, ScienceDirect, and Cochrane Library) were comprehensively searched to identify eligible studies. The strength of association between the Arg264Cys polymorphism and PCa was assessed by pooled odds ratio (OR) and 95% confidence interval (95% CI) in allelic, dominant, recessive, homozygous, and heterozygous genetic models. To analyze the impact of the (TTTA)n repeat polymorphism, we took sequentially the N-repeat allele (where N equals 7,8,10,11,12, and 13) as the minor allele and the sum of all the other alleles as the major allele. The ORs and 95%CIs were calculated in the allelic model; this analysis was performed individually for each repeat number. Results: Pooled estimates of nine studies addressing the Arg264Cys polymorphism indicated that this polymorphism was not associated with PCa risk in the overall population and in the Caucasian and Asian subgroups. The 8-repeat allele in the (TTTA)n repeat polymorphism increased PCa risk in the overall population (OR=1.34, 95% CI=1.14–1.58, P=0.001) and in the subgroup with population-based (PB) controls (OR=1.41, 95% CI=1.13–1.74, P=0.002) as well as in the subgroup of studies using capillary electrophoresis to identify this polymorphism (OR=1.34, 95%CI=1.09-1.65, P=0.006). Conclusions: The meta-analysis indicated that the CYP19A1 (TTTA)n repeat polymorphism, but not Arg264Cys polymorphism may affect PCa risk.

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Aromatase-induced endogenous estrogen promotes tumour metastasis through estrogen receptor-α/matrix metalloproteinase 12 axis activation in castration-resistant prostate cancer

Cited by 21 publications

References 63 publications

Proteoglycans in the Pathogenesis of Hormone-Dependent Cancers: Mediators and Effectors

Proteoglycans in the Pathogenesis of Hormone-Dependent Cancers: Mediators and Effectors

Phosphodiesterase Type-5 Inhibitor Tadalafil Modulates Steroid Hormones Signaling in a Prostate Cancer Cell Line

The CYP19A1 (TTTA)n repeat polymorphism, but not Arg264Cys polymorphism, may affect the risk of prostate cancer: evidence from a meta-analysis

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