Oncogenic Signaling Pathways in Mucopolysaccharidoses
Cancer cells depend on several signaling pathways and organelles, such as the lysosomes. Defects in the activity of lysosomal hydrolases involved in glycosaminoglycan degradation lead to a group of lysosomal storage diseases called Mucopolysaccharidoses (
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1 Postgraduate Program in Genetics and Molecular Biology, UFRGS,
Porto Alegre 91501970, Brazil [email protected] 2 Gene Therapy Center, HCPA, Porto Alegre 90035903, Brazil 3 Bioinformatics Core, HCPA, Porto Alegre 90035903, Brazil 4 Department of Genetics, UFRGS, Porto Alegre 91501970, Brazil 5 Graduation Program on Biotechnology/Bioinformatics, UFRGS, Porto Alegre 91501-970, Brazil
Abstract. Cancer cells depend on several signaling pathways and organelles, such as the lysosomes. Defects in the activity of lysosomal hydrolases involved in glycosaminoglycan degradation lead to a group of lysosomal storage diseases called Mucopolysaccharidoses (MPS). In MPS, secondary cell disturbance affects pathways common to cancer. This work aims to identify oncogenic pathways related to cancer in the different MPS datasets available in public databases and compare the ontologies across the different types of MPS. For this, we used 12 expression datasets of 6 types of MPS. Statistical analysis was based on hypergeometric distribution followed by FDR correction. We found several enriched pathways across the 12 MPS studies, among being 57.65% were KEGG pathways, 32.5% of GO Biological Process, 2.5% GO Celular Component, and 7.35% GO Molecular Function. Hippo signaling pathway and MAPK signaling pathway appear in all datasets. Proteoglycans in cancer, Rap1 signaling pathway, and Cytokinemediated signaling pathway appears in 11 of 12 datasets. The lysosome participates in several biological processes, like autophagy, cell adhesion and migration, and antigen presentation. These processes also may affect in several types of cancer and Lysosomal Storage Diseases. Studying the tumor ontology signature in lysosomal disorders may help understand lysosomal storage diseases and cancer’s underlying mechanisms. This may help amplify therapeutic approaches for both types of diseases. Keywords: Cancer pathways · Gene ontology · Lysosomal storage diseases
1 Introduction Several metabolic pathways are deranged in cancer cells. The proliferation ability of tumors depends on a cascade of signaling pathways in several cancer cells’ organelles, such as the lysosomes [1]. Lysosomes are cellular compartments responsible, among © Springer Nature Switzerland AG 2020 J. C. Setubal and W. M. Silva (Eds.): BSB 2020, LNBI 12558, pp. 259–264, 2020. https://doi.org/10.1007/978-3-030-65775-8_24
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other functions, for the degradation of macromolecules through acid hydrolases contained within them. Defects in these enzymes culminate in the lysosomal accumulation of intermediate metabolites or macromolecules, known as lysosomal storage diseases [2]. Lysosomal Storage Diseases (LSD) are a group of more than 50 rare metabolic diseases, among which we can highlight the Mucopolysaccharidoses (MPS). In MPS, secondary cell disturbance affects pathways common to cancer. This work aims to identify oncogenic pathways related to cancer in the different datasets of MPS available in public databases and to compare the ontologies across the di
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