The small leucine rich proteoglycan fibromodulin is overexpressed in human prostate epithelial cancer cell lines in culture and human prostate cancer tissue

Reyes, Niradiz; Benedetti, Inés; Bettin, Alfonso; Rebollo, Juan; Geliebter, Jan

doi:10.3233/cbm-150555

Cited by 18 publications

(11 citation statements)

References 31 publications

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“…Elevated expression of FMOD has been associated with several types of cancer (Mayr et al, 2005; Reyes et al, 2016), and differential expression of FMOD has been observed in other pathophysiological conditions as well. Yet little was known about the molecular and cellular mechanisms by which FMOD expression is regulated, and only one study has been reported which suggested that FMOD transcription in glioma cells is positively regulated by the TGF-β1/SMAD2 pathway by an epigenetic mechanism (Mondal et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…In a carcinoma model, FMOD controls the stoma matrix structure which affects the internal and external fluid stability of the carcinoma stroma (Oldberg et al, 2007). FMOD was suggested to be a tumor-associated antigen in chronic lymphocytic leukemia (CLL) (Mayr et al, 2005); in clinical samples obtained from prostate cancer patients, significant variations of FMOD expression were observed between benign and malignant tissues (Reyes et al, 2016); and a recent study implicated FMOD in glioma cell migration (Mondal et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

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Wnt/β-Catenin Pathway-Regulated Fibromodulin Expression Is Crucial for Breast Cancer Metastasis and Inhibited by Aspirin

et al. 2019

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Emerging evidence suggests that fibromodulin (FMOD), an extracellular matrix protein, is associated with cancer, and yet little is known about the regulation of FMOD expression and its role in cancer metastasis. Aspirin, a classic anti-inflammatory drug, has been indicated to offer anticancer benefits, but its action targets and mechanisms remain obscure. In the present study using cell lines, animal model and database analysis, we show that FMOD is crucial for breast cancer cell migration and invasion (BCCMI) via activation of ERK; expression of FMOD is regulated positively by the Wnt/β-catenin pathway, wherein the β-catenin/TCF4/LEF1 complex binds the FMOD promoter to transcribe FMOD. Aspirin inhibits BCCMI by attenuating Wnt/β-catenin signaling and suppressing FMOD expression via inhibiting deacetylation of β-catenin by histone deacetylase 6 (HDAC6) leading to β-catenin phosphorylation and cytoplasmic degradation. Moreover, expression of the transcriptional complex components β-catenin/TCF4/LEF1 is upregulated by the Wnt/β-catenin pathway, constituting positive feedback loops that amplify its signal output. Our findings identify a critical role of FMOD in cancer metastasis, reveal a mechanism regulating FMOD transcription and impacting tumor metastasis, uncover action targets and mechanism for the anticancer activity of Aspirin, and expand the understanding of the Wnt/β-catenin pathway and tumor metastasis, which are valuable for development of cancer therapeutics.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Wnt/β-Catenin Pathway-Regulated Fibromodulin Expression Is Crucial for Breast Cancer Metastasis and Inhibited by Aspirin

et al. 2019

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“…Recently, it was shown that the SLRP fibromodulin has discrete expression among PC and benign tissues [ 58 ]. PC tissues express this PG, as do PC cell lines with, interestingly, the highest expression determined in the androgen-sensitive human metastatic prostate adenocarcinoma LNCaP clone [ 59 ]. Moreover, the glypican-1 expression in urine cell sediments was proposed as a possible positive marker for PC [ 60 ].…”

Section: Proteoglycan Expression In Hormone-dependent Cancermentioning

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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“…Tumour cells release growth factors and angiogenic factors which play a crucial role in tumour progression, angiogenesis and LVI. Lymphatic endothelial cells, in turn, interact with tumour cells, resulting in the secretion of small leucine-rich repeat proteoglycan, thus stimulating tumour cells to metastasise [13, 14]. However, the key molecular mechanisms underlying LVI, whether the alterations are in the tumour cells, in the endothelial cells or in both remain to be deciphered.…”

Section: Introductionmentioning

confidence: 99%

Molecular Complexity of Lymphovascular Invasion: The Role of Cell Migration in Breast Cancer as a Prototype

et al. 2020

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Lymphovascular invasion (LVI) is associated with poor outcome in breast cancer (BC); however, its underlying mechanisms remain ill-defined. LVI in BC develops through complex molecular pathways involving not only the interplay with the surrounding microenvironment along with endothelial cells lining the lymphovascular spaces but also changes in the malignant epithelial cells with the acquisition of more invasive and migration abilities. In this review, we focus on the key features that enable tumour cell detachment from the primary niche, their migration and interaction with the surrounding microenvironment as well as the crosstalk with the vascular endothelial cells, which eventually lead to intravasation of tumour cells and LVI. Intravascular tumour cell survival and migration, their distant site extravasation, stromal invasion and growth are part of the metastatic cascade. Cancer cell migration commences with loss of tumour cells' cohesion initiating the invasion and migration processes which are usually accompanied by the accumulation of specific cellular and molecular changes that enable tumour cells to overcome the blockades of the extracellular matrix, spread into surrounding tissues and interact with stromal cells and immune cells. Thereafter, tumour cells migrate further via interacting with lymphovascular endothelial cells to penetrate the vessel wall leading ultimately to intravasation of cancer cells. Exploring the potential factors influencing cell migration in LVI can help in understanding the underlying mechanisms of LVI to identify targeted therapy in BC.

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The small leucine rich proteoglycan fibromodulin is overexpressed in human prostate epithelial cancer cell lines in culture and human prostate cancer tissue

Cited by 18 publications

References 31 publications

Wnt/β-Catenin Pathway-Regulated Fibromodulin Expression Is Crucial for Breast Cancer Metastasis and Inhibited by Aspirin

Wnt/β-Catenin Pathway-Regulated Fibromodulin Expression Is Crucial for Breast Cancer Metastasis and Inhibited by Aspirin

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

Molecular Complexity of Lymphovascular Invasion: The Role of Cell Migration in Breast Cancer as a Prototype

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