Abnormal Glycosylation of Cancer Stem Cells and Targeting Strategies

Khan, Thahomina; Cabral, Horacio

doi:10.3389/fonc.2021.649338

Cited by 19 publications

(17 citation statements)

References 163 publications

(183 reference statements)

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“…CSC-like features can be controlled in various ways. Post-transcriptional modifications, especially glycolsylation, have been reported to contribute significantly to CSC-like features in several cancers [19]. Glycosylation is a common post-translational modification of membrane-related and secreted proteins [20].…”

Section: Discussionmentioning

confidence: 99%

A novel ALG10/TGF-β positive regulatory loop contributes to the stemness of colorectal cancer

Wang

et al. 2022

Aging

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The roles of asparagine-linked glycosylation (ALG) members in tumorigenic process have been widely explored. However, their effects in colorectal cancer progression are still confusing. Here, we screened 12 ALGs' expression through online datasets and found that ALG10 was mostly upregulated in colorectal cancer tissues. We found that ALG10 knockdown significantly suppressed the expression of stemness markers, ALDH activity, and sphere-formation ability. In vivo tumorigenic analysis indicated that ALG10 knockdown attenuated the tumor-initiating ability and chemoresistance of colorectal cancer cells. Further mechanistic studies showed that ALG10 knockdown suppressed the activity of TGF-β signaling by reducing TGFBR2 glycosylation, which was necessary for ALG10-mediated effects on colorectal cancer stemness; Conversely, TGF-β signaling activated ALG10 gene promoter activity through Smad2's binding to ALG10 gene promoter and TGF-β signaling promoted the stemness of colorectal cancer cells in an ALG10-dependent manner. This work identified a novel ALG10/TGF-β positive regulatory loop responsible for colorectal cancer stemness.

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Section: Discussionmentioning

confidence: 99%

A novel ALG10/TGF-β positive regulatory loop contributes to the stemness of colorectal cancer

Wang

et al. 2022

Aging

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“…It has been well documented that aberrant glycosylation contributes to tumorigenesis in multiple cancer types [18][19][20]. In addition, aberrant glycosylation increased cancer stem cell ability for tumour proliferation [21] and also could weakened immune checkpoint blockade against cancer cells [22,23]. Simultaneously, accumulating data showed that protein glycosylation and trafficking were regulated by the conserved oligomeric Golgi (COG) complex [24].…”

Section: Discussionmentioning

confidence: 99%

Abnormal Expression and Prognosis Value of COG Complex Members in Kidney Renal Clear Cell Carcinoma (KIRC)

2021

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Kidney renal clear cell carcinoma (KIRC) is the most aggressive subtype of kidney tumours with poor prognosis as well as the increasing incidence rate in worldwide. The conserved oligomeric Golgi (COG) complex is an eight-subunit (Cog1-8) peripheral Golgi protein that controls membrane trafficking and protein glycosylation and plays vital roles in human disease including cancers. Therefore, to uncover the prognostic value of COG complex in KIRC, a series of databases, including UALCAN database, GEPIA database, and Kaplan-Meier plotter, were used to analyse the mRNA expression of COG complex subunits and their prognostic values in patients with KIRC in this study. Compared with normal counterparts, mRNA expression of six COG complex subunits was significantly downregulated in KIRC tissue in UALCAN database, while COG4 mRNA expression was significantly upregulated in KIRC tissue. Moreover, the survival analysis indicated that all members of COG complex subunits were closely related with the prognosis of KIRC patients, while COG1 and COG4 were significantly associated with unfavourable overall survival (OS), the rest of COG complex subunits were importantly correlated with favourable OS. Simultaneously, higher mRNA expression of COG3, COG6, and COG8 exhibits better progression-free survival (PFS) and disease-free survival (DFS) in KIRC patients. These results identified that COG complex subunits, especially COG3, COG6, and COG8, are potential prognostic biomarkers of KIRC patients and may offer effective and new strategies for more accurately diagnosing the patients with KIRC in advance.

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“…As nicely summarized by Khan and Cabral, the aberrant glycosylation of markers of cancer stem cells (CSCs) in key cellular signaling pathways has been directly correlated with the self-renewal properties and drug-resistant mechanisms [135]. The Tian group performed site-specific N-glycoproteomics to characterize the differential N-glycosylation in MCF-7 cancer stem cells relative to MCF-7 cells, leading to the discovery of potential N-glycoprotein markers of MCF-7 cancer stem cells [30].…”

Section: Cancers and Other Diseasesmentioning

confidence: 99%

Strategies for Proteome-Wide Quantification of Glycosylation Macro- and Micro-Heterogeneity

Pan

Oellerich

et al. 2022

IJMS

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Protein glycosylation governs key physiological and pathological processes in human cells. Aberrant glycosylation is thus closely associated with disease progression. Mass spectrometry (MS)-based glycoproteomics has emerged as an indispensable tool for investigating glycosylation changes in biological samples with high sensitivity. Following rapid improvements in methodologies for reliable intact glycopeptide identification, site-specific quantification of glycopeptide macro- and micro-heterogeneity at the proteome scale has become an urgent need for exploring glycosylation regulations. Here, we summarize recent advances in N- and O-linked glycoproteomic quantification strategies and discuss their limitations. We further describe a strategy to propagate MS data for multilayered glycopeptide quantification, enabling a more comprehensive examination of global and site-specific glycosylation changes. Altogether, we show how quantitative glycoproteomics methods explore glycosylation regulation in human diseases and promote the discovery of biomarkers and therapeutic targets.

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Abnormal Glycosylation of Cancer Stem Cells and Targeting Strategies

Cited by 19 publications

References 163 publications

A novel ALG10/TGF-β positive regulatory loop contributes to the stemness of colorectal cancer

A novel ALG10/TGF-β positive regulatory loop contributes to the stemness of colorectal cancer

Abnormal Expression and Prognosis Value of COG Complex Members in Kidney Renal Clear Cell Carcinoma (KIRC)

Strategies for Proteome-Wide Quantification of Glycosylation Macro- and Micro-Heterogeneity

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