Syndecan-4 is a maestro of gastric cancer cell invasion and communication that underscores poor survival

Poças, Juliana; Marques, Catarina; Gomes, Catarina; Otake, Andréia Hanada; Pinto, Filipe; Ferreira, Mariana; Silva, Tiago; Faria‐Ramos, Isabel; Matos, Rita; Ribeiro, Ana Thaís Martins Carvalho; Senra, Emanuel; Cavadas, Bruno; Batista, Sílvia; Maia, Joana; Macedo, Joana A.; Lima, Luís; Afonso, Luís Pedro; Ferreira, José Alexandre; Santos, Lúcio Lara; Polónia, António; Osório, Hugo; Belting, Mattias; Reis, Celso A.; Costa-Silva, Bruno; Magalhães, Ana

doi:10.1073/pnas.2214853120

Cited by 16 publications

(6 citation statements)

References 71 publications

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“…In agreement with these earlier reports, subsequent studies utilizing R software and quantitative Real-Time PCR analysis, together with a comprehensive meta-analysis of gene expression profiles and gastric cancer patient's clinical data from the Cancer Genome Atlas database, demonstrated substantial variation in lumican expression when comparing gastric cancer tissues and adjacent healthy tissues [91,92]. Notably, other PGs, including the cell membrane HSPG syndecan-4, are overexpressed in gastric cancer [93]. Indeed, syndecan-4 overexpression has been correlated with poor patient prognosis.…”

Section: Biglycan and Lumican Expression And Roles In Cancerogenesissupporting

confidence: 79%

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The Landscape of Small Leucine-Rich Proteoglycan Impact on Cancer Pathogenesis with a Focus on Biglycan and Lumican

Berdiaki

Giatagana

Tzanakakis

et al. 2023

Cancers

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Cancer development is a multifactorial procedure that involves changes in the cell microenvironment and specific modulations in cell functions. A tumor microenvironment contains tumor cells, non-malignant cells, blood vessels, cells of the immune system, stromal cells, and the extracellular matrix (ECM). The small leucine-rich proteoglycans (SLRPs) are a family of nineteen proteoglycans, which are ubiquitously expressed among mammalian tissues and especially abundant in the ECM. SLRPs are divided into five canonical classes (classes I–III, containing fourteen members) and non-canonical classes (classes IV–V, including five members) based on their amino-acid structural sequence, chromosomal organization, and functional properties. Variations in both the protein core structure and glycosylation status lead to SLRP-specific interactions with cell membrane receptors, cytokines, growth factors, and structural ECM molecules. SLRPs have been implicated in the regulation of cancer growth, motility, and invasion, as well as in cancer-associated inflammation and autophagy, highlighting their crucial role in the processes of carcinogenesis. Except for the class I SLRP decorin, to which an anti-tumorigenic role has been attributed, other SLPRs’ roles have not been fully clarified. This review will focus on the functions of the class I and II SLRP members biglycan and lumican, which are correlated to various aspects of cancer development.

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Section: Biglycan and Lumican Expression And Roles In Cancerogenesissupporting

confidence: 79%

“…Indeed, syndecan-4 overexpression has been correlated with poor patient prognosis. Syndecan 4 is suggested to modulate gastric cancer cells' invasion and motility [93]. Likewise, prospective studies must be performed to validate lumican as a prognostic marker in gastric cancer.…”

Section: Biglycan and Lumican Expression And Roles In Cancerogenesismentioning

confidence: 99%

The Landscape of Small Leucine-Rich Proteoglycan Impact on Cancer Pathogenesis with a Focus on Biglycan and Lumican

Berdiaki

Giatagana

Tzanakakis

et al. 2023

Cancers

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“…Indeed, there has been a growing body of evidence suggesting the role of glycosylation in EV biology, namely affecting their uptake by recipient cells and regulating organ tropism. [ 57 , 58 , 59 ] Considering the multitude of glycosyltransferases that regulate the glycosylation pathway, [ 18 ] it is crucial to understand how cellular architecture affects the expression of these enzymes that would impact not only the cell glycome but also the glycome of their secreted EVs.…”

Section: Discussionmentioning

confidence: 99%

Differential Protein and Glycan Packaging into Extracellular Vesicles in Response to 3D Gastric Cancer Cellular Organization

et al. 2023

Self Cite

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Alterations of the glycosylation machinery are common events in cancer, leading to the synthesis of aberrant glycan structures by tumor cells. Extracellular vesicles (EVs) play a modulatory role in cancer communication and progression, and interestingly, several tumor‐associated glycans have already been identified in cancer EVs. Nevertheless, the impact of 3D tumor architecture in the selective packaging of cellular glycans into EVs has never been addressed. In this work, the capacity of gastric cancer cell lines with differential glycosylation is evaluated in producing and releasing EVs when cultured under conventional 2D monolayer or in 3D culture conditions. Furthermore, the proteomic content is identified and specific glycans are studied in the EVs produced by these cells, upon differential spatial organization. Here, it is observed that although the proteome of the analyzed EVs is mostly conserved, an EV differential packaging of specific proteins and glycans is found. In addition, protein–protein interaction and pathway analysis reveal individual signatures on the EVs released by 2D‐ and 3D‐cultured cells, suggesting distinct biological functions. These protein signatures also show a correlation with clinical data. Overall, this data highlight the importance of tumor cellular architecture when assessing the cancer‐EV cargo and its biological role.

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“…The integrin α5β1 cross-talks with syndecans through a cytosolic molecular bridge, between paxillin and syndesmos, generating cooperative signaling between these receptors ( Kusano et al, 2000 ; Denhez et al, 2002 ; Bass et al, 2007 ; Chronopoulos et al, 2020 ; Ahn et al, 2023 ). Interestingly, the levels of syndecans in cancer cells correlate with tumor size, invasiveness, and metastatic capacity ( Kim et al, 2015 ; Poças et al, 2023 ). Many of these actions are considered a consequence of the cooperation with integrins ( Beauvais and Rapraeger, 2004 ; Choi et al, 2013 ).…”

Section: Cell Receptors Binding Fn Play a Pivotal Role As Primary Mec...mentioning

confidence: 99%

Shaping Oncogenic Microenvironments: Contribution of Fibronectin

Guerrero-Barberà,

Burday,

Costell

2024

Front. Cell Dev. Biol.

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The extracellular matrix (ECM) is a complex network of proteins and glycans, dynamically remodeled and specifically tailored to the structure/function of each organ. The malignant transformation of cancer cells is determined by both cell intrinsic properties, such as mutations, and extrinsic variables, such as the mixture of surrounding cells in the tumor microenvironment and the biophysics of the ECM. During cancer progression, the ECM undergoes extensive remodeling, characterized by disruption of the basal lamina, vascular endothelial cell invasion, and development of fibrosis in and around the tumor cells resulting in increased tissue stiffness. This enhanced rigidity leads to aberrant mechanotransduction and further malignant transformation potentiating the de-differentiation, proliferation and invasion of tumor cells. Interestingly, this fibrotic microenvironment is primarily secreted and assembled by non-cancerous cells. Among them, the cancer-associated fibroblasts (CAFs) play a central role. CAFs massively produce fibronectin together with type I collagen. This review delves into the primary interactions and signaling pathways through which fibronectin can support tumorigenesis and metastasis, aiming to provide critical molecular insights for better therapy response prediction.

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Syndecan-4 is a maestro of gastric cancer cell invasion and communication that underscores poor survival

Cited by 16 publications

References 71 publications

The Landscape of Small Leucine-Rich Proteoglycan Impact on Cancer Pathogenesis with a Focus on Biglycan and Lumican

The Landscape of Small Leucine-Rich Proteoglycan Impact on Cancer Pathogenesis with a Focus on Biglycan and Lumican

Differential Protein and Glycan Packaging into Extracellular Vesicles in Response to 3D Gastric Cancer Cellular Organization

Shaping Oncogenic Microenvironments: Contribution of Fibronectin

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