The Role of Glypicans in Cancer Progression and Therapy

Li, Nan; Spetz, Madeline R.; Ho, Mitchell

doi:10.1369/0022155420933709

Cited by 53 publications

(48 citation statements)

References 194 publications

(245 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…High expression of GPC2 has been detected in neuroblastoma and other pediatric cancers such as medulloblastoma and retinoblastoma [124,125]. While CPG3 results in being overexpressed in liver cancer, lung squamous cell carcinoma, neuroblastoma, ovarian cancer, testicular germ cell tumor, thyroid cancer, yolk sac tumor and other cancers, reduced levels of GPC3 have been found in breast cancer, colorectal cancer, mesothelioma, non-small-cell lung cancer, neuroblastoma, and renal cell carcinoma [35,105,[125][126][127][128][129][130]. Overexpression of GPC4 mRNA has been detected in metastatic colorectal cancer, where GPC1, GPC3 and GPC6, perlecan, and collagen type VIII result in being downregulated [31,35,105].…”

Section: Collagen Type VIII Col8a1mentioning

confidence: 99%

“…The HS chain of HSPGs binds the FGF ligand and receptor forming a ternary complex that promotes FGFR dimerization, and in turn activates signaling. Depending on the tumor type, HSPG-regulated FGF binding and receptor dimerization triggers the activation of four main signaling pathways, including mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT), Janus kinase (JAK)/signal transducer and activator of transcription (STAT), and protein kinase C (PKC) pathways [15,35,125,170]. However, other HSPG-mediated FGF/FGFR downstream signaling, such as Jun N-terminal kinase (JNK), ribosomal protein S6 kinase 2 (RSK2), and Rho GTPase pathways, have been described to play a role in some cancers [35,125,[171][172][173].…”

Section: Hspg-regulated Mechanisms In Cell-matrix and Cell-cell Intermentioning

confidence: 99%

“…However, a significant reduction of cell surface tethered SDC1 and an increase of shed SDC1 in the ECM has been observed as a function of tumor progression and aggressiveness, suggesting the involvement of post-transcriptional mechanisms in SDC1 expression in this type of tumor. Differential regulation of SDC1 expression as well as of the other SDC isoforms, GPCs, and the other HSPGs has been found in several tumors ( Table 3 ) [ 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 ].…”

Section: Structural Features Biosynthesis and Enzymatic Modificamentioning

confidence: 99%

See 2 more Smart Citations

Heparan Sulfate Proteoglycan Signaling in Tumor Microenvironment

Pasquale

Pavone

2020

IJMS

View full text Add to dashboard Cite

In the last few decades, heparan sulfate (HS) proteoglycans (HSPGs) have been an intriguing subject of study for their complex structural characteristics, their finely regulated biosynthetic machinery, and the wide range of functions they perform in living organisms from development to adulthood. From these studies, key roles of HSPGs in tumor initiation and progression have emerged, so that they are currently being explored as potential biomarkers and therapeutic targets for cancers. The multifaceted nature of HSPG structure/activity translates in their capacity to act either as inhibitors or promoters of tumor growth and invasion depending on the tumor type. Deregulation of HSPGs resulting in malignancy may be due to either their abnormal expression levels or changes in their structure and functions as a result of the altered activity of their biosynthetic or remodeling enzymes. Indeed, in the tumor microenvironment, HSPGs undergo structural alterations, through the shedding of proteoglycan ectodomain from the cell surface or the fragmentation and/or desulfation of HS chains, affecting HSPG function with significant impact on the molecular interactions between cancer cells and their microenvironment, and tumor cell behavior. Here, we overview the structural and functional features of HSPGs and their signaling in the tumor environment which contributes to tumorigenesis and cancer progression.

show abstract

Section: Collagen Type VIII Col8a1mentioning

confidence: 99%

Section: Hspg-regulated Mechanisms In Cell-matrix and Cell-cell Intermentioning

confidence: 99%

Section: Structural Features Biosynthesis and Enzymatic Modificamentioning

confidence: 99%

See 1 more Smart Citation

Heparan Sulfate Proteoglycan Signaling in Tumor Microenvironment

Pasquale

Pavone

2020

IJMS

View full text Add to dashboard Cite

show abstract

“…GPCs have been receiving great attention from the research community as promising biomarkers [ 262 ]. GPC1 is overexpressed in several cancer types [ 263 , 264 ].…”

Section: Heparan Sulfate Clinical Applications–recent Advancesmentioning

confidence: 99%

Heparan Sulfate Glycosaminoglycans: (Un)Expected Allies in Cancer Clinical Management

et al. 2021

View full text Add to dashboard Cite

In an era when cancer glycobiology research is exponentially growing, we are witnessing a progressive translation of the major scientific findings to the clinical practice with the overarching aim of improving cancer patients’ management. Many mechanistic cell biology studies have demonstrated that heparan sulfate (HS) glycosaminoglycans are key molecules responsible for several molecular and biochemical processes, impacting extracellular matrix properties and cellular functions. HS can interact with a myriad of different ligands, and therefore, hold a pleiotropic role in regulating the activity of important cellular receptors and downstream signalling pathways. The aberrant expression of HS glycan chains in tumours determines main malignant features, such as cancer cell proliferation, angiogenesis, invasion and metastasis. In this review, we devote particular attention to HS biological activities, its expression profile and modulation in cancer. Moreover, we highlight HS clinical potential to improve both diagnosis and prognosis of cancer, either as HS-based biomarkers or as therapeutic targets.

show abstract

“…Syndecans are the most represented family of transmembrane HSPGs [ 30 ], and their cytoplasmic domain can interact with the cytoskeleton and can transduce a signal inside the cell upon binding with their extracellular ligands [ 31 ]. Glypicans are instead GPI-anchored HSPGs whose main function is to facilitate and/or stabilize the interaction of different cytokines and growth factors with their receptors and to transport cargoes into and through cells for their recycling [ 32 ]. Perlecan and agrin are the two most prevalent PGs in the basement membranes, but they can be also found at the cell surface, anchored to integrins or other receptors [ 16 ].…”

Section: Fundamentals Of Gags and Pgsmentioning

confidence: 99%

A Bittersweet Computational Journey among Glycosaminoglycans

et al. 2021

View full text Add to dashboard Cite

Glycosaminoglycans (GAGs) are linear polysaccharides. In proteoglycans (PGs), they are attached to a core protein. GAGs and PGs can be found as free molecules, associated with the extracellular matrix or expressed on the cell membrane. They play a role in the regulation of a wide array of physiological and pathological processes by binding to different proteins, thus modulating their structure and function, and their concentration and availability in the microenvironment. Unfortunately, the enormous structural diversity of GAGs/PGs has hampered the development of dedicated analytical technologies and experimental models. Similarly, computational approaches (in particular, molecular modeling, docking and dynamics simulations) have not been fully exploited in glycobiology, despite their potential to demystify the complexity of GAGs/PGs at a structural and functional level. Here, we review the state-of-the art of computational approaches to studying GAGs/PGs with the aim of pointing out the “bitter” and “sweet” aspects of this field of research. Furthermore, we attempt to bridge the gap between bioinformatics and glycobiology, which have so far been kept apart by conceptual and technical differences. For this purpose, we provide computational scientists and glycobiologists with the fundamentals of these two fields of research, with the aim of creating opportunities for their combined exploitation, and thereby contributing to a substantial improvement in scientific knowledge.

show abstract

The Role of Glypicans in Cancer Progression and Therapy

Cited by 53 publications

References 194 publications

Heparan Sulfate Proteoglycan Signaling in Tumor Microenvironment

Heparan Sulfate Proteoglycan Signaling in Tumor Microenvironment

Heparan Sulfate Glycosaminoglycans: (Un)Expected Allies in Cancer Clinical Management

A Bittersweet Computational Journey among Glycosaminoglycans

Contact Info

Product

Resources

About