Metal ions and the extracellular matrix in tumor migration

Stelling, Mariana P.; Motta, Juliana María; Mashid, Marjon; Johnson, Wyatt E.; Pavão, Mauro S.G.; Farrell, Nicholas

doi:10.1111/febs.14986

Cited by 41 publications

(31 citation statements)

References 130 publications

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“…In case of breast cancer tissue, PC3 and PC6 explained 8.47% and 1.53% of variance of image features and were associated with GO terms such as response to metal ion and response to hypoxia, respectively. It has been reported that metal ions along with glycosaminoglycan in extracellular matrix affect angiogenesis and cancer cell migration via integrin activation 24 . In addition, hypoxia play a key role in tumor progression by hypoxia inducible factor (HIF) pathway and promotes angiogenesis and epithelial-to-mesenchymal transition 25 .…”

Section: Discussionmentioning

confidence: 99%

Discovery of molecular features underlying morphological landscape by integrating spatial transcriptomic data with deep features of tissue image

Bae

Choi

Lee

2020

Preprint

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Profiling molecular features associated with the morphological landscape of tissue is crucial to interrogate structural and spatial patterns that underlie biological function of tissues.Here, we present a new method, SPADE, to identify important genes associated with morphological contexts by combining spatial transcriptomic data with co-registered images.SPADE incorporates deep learning-derived image patterns with spatially resolved gene expression data to extract morphological context markers. Morphological features that correspond to spatial maps of transcriptome were extracted by image patches surrounding each spot, and then, represented by image latent features. The molecular profiles correlated with the image latent features were identified. The extracted genes could be further analyzed to discover functional terms and also exploited to extract clusters maintaining morphological contexts. We apply our approach to spatial transcriptomic data of three different tissues to suggest an unbiased method capable of offering image-integrated gene expression trends.

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Section: Discussionmentioning

confidence: 99%

Discovery of molecular features underlying morphological landscape by integrating spatial transcriptomic data with deep features of tissue image

Bae

Choi

Lee

2020

Preprint

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“…Thus, considering this principle and according to the gene ontology (GO) terms enrichment analyses, LINC00968 might be involved in some biological processes like vasculature development, blood vessel development, cardiovascular system development, extracellular matrix organization, and angiogenesis. Angiogenesis is an important process in the development of new blood vessels, and invasion and metastasis of tumor cells [37]. The vascular ECM is consisted of the basement membrane and the interstitial ECM that have major functions in vascular homeostasis and tumor angiogenesis [38].…”

Section: Discussionmentioning

confidence: 99%

“…Also, the functional analyses indicated that LINC00968 is mostly involved in glycosaminoglycan binding, heparin binding, calcium ion binding, and extracellular matrix structural constituent. Glycosaminoglycans (GAGs) are components of the extracellular matrix (ECM) that are contributed in the regulation of cell functions [37]. ECM constituents are critical in molecular and cellular mechanisms of cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…Interaction between molecules expressed by cancer cells and factors in tumor microenvironment can affect tumor cell survival, proliferation of tumor cells, adhesion, migration of tumor cells, and therefore, tumor invasion and metastasis [39]. Calcium and some ECM components like Glycosaminoglycans (GAGs) have interaction with each other and imbalance of extracellular concentrations of some ions like calcium can promote or suppress cancer cell migration [37].…”

Section: Discussionmentioning

confidence: 99%

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Potential role of long non-coding RNA LINC00968 in luminal A and B breast cancers

Arabpour

Layeghi

Majidzadeh‐A

et al. 2020

Preprint

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Purpose Breast Cancer (BC) is the most frequent malignancy among women worldwide. ER+ breast cancers (luminal A and B subtypes) comprise up to 70% of all BC patients. Long non-coding RNAs (lncRNAs) are regulatory non-coding transcripts and longer than 200 nucleotides. LncRNAs can affect many biological and pathological processes and dysregulation of them is related to many human cancers. The potential role of LINC00968 lncRNA in luminal A and B breast cancer pathogenesis is still unclear. Methods Seventy-one pairs of tumor and adjacent non-tumor tissue specimens of luminal A and B breast cancer were used to analyze the expression of LINC00968. Furthermore, two luminal A cell lines, MCF7 and T47D, were used to evaluate the expression of LINC00968 compared with a non-malignant breast cell line, MCF10A. Moreover, we have done multiple bioinformatic analyses for a better understanding of the potential roles of LINC00968 in luminal BC. Results Our data revealed the significant downregulation of LINC00968 in luminal tumor tissues and cell lines. LINC00968 expression was negatively associated with tumor stage and lymph node metastasis. Bioinformatic analyses indicated that LINC00968 might be involved in blood vessel development, angiogenesis, and might be participated in interaction of ECM constituents with cancer cells. LINC00968 might have functions in some cancer-related signaling pathways, like PI3K/Akt, ECM-receptor interaction signaling pathway, and PPAR signaling pathway. Conclusions Downregulation of LINC00968 might promote carcinogenesis of luminal BC. LINC00968 might act as a tumor suppressor gene and might also promote invasion and metastasis of luminal BC.

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“…85 The binding of prion protein to GAGs is stabilized by Cu 2+ or Zn 2+ ions, and the interaction of endostatin with HS is increased in the presence of Zn 2+ ions. 86 In addition, HP binds to calcium, 85 which plays a major role in ECM assembly and functions, 87 and in ECM-cell interactions 88 as reported for syndecans, which interact with transient receptor potential channels involved in Ca 2+ entry mechanisms and can regulate them. 89 Here again, modeling approaches could provide new insights on the effects of ions on protein-GAG interactions as shown for the complex formed by the ECM protein procollagen C-proteinase enhancer-1 and GAG oligosaccharides.…”

Section: The First Draft Of the Glycosaminoglycan Interactomementioning

confidence: 99%

Glycosaminoglycan–Protein Interactions: The First Draft of the Glycosaminoglycan Interactome

Vallet

Clerc

Ricard‐Blum

2020

J Histochem Cytochem.

125

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The six mammalian glycosaminoglycans (GAGs), chondroitin sulfate, dermatan sulfate, heparin, heparan sulfate, hyaluronan, and keratan sulfate, are linear polysaccharides. Except for hyaluronan, they are sulfated to various extent, and covalently attached to proteins to form proteoglycans. GAGs interact with growth factors, morphogens, chemokines, extracellular matrix proteins and their bioactive fragments, receptors, lipoproteins, and pathogens. These interactions mediate their functions, from embryonic development to extracellular matrix assembly and regulation of cell signaling in various physiological and pathological contexts such as angiogenesis, cancer, neurodegenerative diseases, and infections. We give an overview of GAG–protein interactions (i.e., specificity and chemical features of GAG- and protein-binding sequences), and review the available GAG–protein interaction networks. We also provide the first comprehensive draft of the GAG interactome composed of 832 biomolecules (827 proteins and five GAGs) and 932 protein–GAG interactions. This network is a scaffold, which in the future should integrate structures of GAG–protein complexes, quantitative data of the abundance of GAGs in tissues to build tissue-specific interactomes, and GAG interactions with metal ions such as calcium, which plays a major role in the assembly of the extracellular matrix and its interactions with cells. This contextualized interactome will be useful to identify druggable GAG–protein interactions for therapeutic purpose:

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Metal ions and the extracellular matrix in tumor migration

Cited by 41 publications

References 130 publications

Discovery of molecular features underlying morphological landscape by integrating spatial transcriptomic data with deep features of tissue image

Discovery of molecular features underlying morphological landscape by integrating spatial transcriptomic data with deep features of tissue image

Potential role of long non-coding RNA LINC00968 in luminal A and B breast cancers

Glycosaminoglycan–Protein Interactions: The First Draft of the Glycosaminoglycan Interactome

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