Ganglioside GM2: a potential biomarker for cholangiocarcinoma

Talabnin, Krajang; Talabnin, Chutima; Kumagai, Tadashi; Sutatum, Nuchanard; Khiaowichit, Juthamas; Dechsukhum, Chawaboon; Ishihara, Mayumi; Azadi, Parastoo; Sripa, Banchob

doi:10.1177/0300060520903216

Cited by 9 publications

(5 citation statements)

References 29 publications

(33 reference statements)

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“…The results suggest that aberrant expression of ceramide-metabolizing enzymes occurs in CCA. Additionally, high GCS expression in CCA is consistent with the studies on lipidomic measurements in CCA tissues, in which high levels of hexosylceramides and lactosylceramides are observed in CCA tissues, and these levels were associated with short survival of the CCA patients [ 34 , 35 ]. Up-regulation of GCS is implicated in cancer progression and multi-drug resistance, but the role of glucosylceramide breakdown (including GBA1 and GBA2) in cancer is unclear.…”

Section: Discussionsupporting

confidence: 84%

Inhibition of Ceramide Glycosylation Enhances Cisplatin Sensitivity in Cholangiocarcinoma by Limiting the Activation of the ERK Signaling Pathway

Chueakwon

Jatooratthawichot

Talabnin

et al. 2022

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Cholangiocarcinoma (CCA) is an aggressive tumor of the biliary epithelium with poor survival that shows limited response to conventional chemotherapy. Increased expression of glucosylceramide synthase (GCS) contributes to drug resistance and the progression of various cancers; the expression profiles of GCS (UGCG) and the genes for glucocerebrosidases 1, 2, and 3 (GBA1, GBA2, and GBA3) were therefore studied in CCA. The biological functions of GCS for cell proliferation and cisplatin sensitivity in CCA were explored. GCS expression was higher in CCA tumor tissues than that of GBA1, GBA2, and GBA3. Verification of GCS expression in 29 paired frozen CCA tissues showed that 8 of 29 cases (27.6%) had high GCS expression. The expression of GCS and GBA2 was induced in CCA cell lines following low-dose cisplatin treatment. Suppression of GCS by either palmitoylamino-3-morpholino-1-propanol (PPMP), GCS knockdown or a combination of the two resulted in reduced cell proliferation. These treatments enhanced the effect of cisplatin-induced CCA cell death, increased the expression of apoptotic proteins and reduced phosphorylation of ERK upon cisplatin treatment. Taken together, inhibition of the GCS increased cisplatin-induced CCA apoptosis via the inhibition of the ERK signaling pathway. Thus, targeting GCS might be a strategy for CCA treatment.

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Section: Discussionsupporting

confidence: 84%

Inhibition of Ceramide Glycosylation Enhances Cisplatin Sensitivity in Cholangiocarcinoma by Limiting the Activation of the ERK Signaling Pathway

Chueakwon

Jatooratthawichot

Talabnin

et al. 2022

Life

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“…Here, the authors reported on a gradual increase in GM1, GM2, GM3, GD1, and GD3 species towards malignant tumors [ 137 ]. A similar observation was reported in cholangiocarcinoma, demonstrating that the GM2 concentration was elevated in the serum of patients with cholangiocarcinoma [ 138 ]. Elevated gangliosides in cancer patients were also reported in blood samples in 73 children with high-risk neuroblastoma compared with 40 cancer-free children using LC-TMS.…”

Section: An Overview Of Current Methodologies To Characterize Gslssupporting

confidence: 84%

Deciphering the Importance of Glycosphingolipids on Cellular and Molecular Mechanisms Associated with Epithelial-to-Mesenchymal Transition in Cancer

et al. 2021

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Every living cell is covered with a dense and complex layer of glycans on the cell surface, which have important functions in the interaction between cells and their environment. Glycosphingolipids (GSLs) are glycans linked to lipid molecules that together with sphingolipids, sterols, and proteins form plasma membrane lipid rafts that contribute to membrane integrity and provide specific recognition sites. GSLs are subdivided into three major series (globo-, ganglio-, and neolacto-series) and are synthesized in a non-template driven process by enzymes localized in the ER and Golgi apparatus. Altered glycosylation of lipids are known to be involved in tumor development and metastasis. Metastasis is frequently linked with reversible epithelial-to-mesenchymal transition (EMT), a process involved in tumor progression, and the formation of new distant metastatic sites (mesenchymal-to-epithelial transition or MET). On a single cell basis, cancer cells lose their epithelial features to gain mesenchymal characteristics via mechanisms influenced by the composition of the GSLs on the cell surface. Here, we summarize the literature on GSLs in the context of reversible and cancer-associated EMT and discuss how the modification of GSLs at the cell surface may promote this process.

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“…Hence, specific gangliosides are associated with certain kinds of cancer and have therefore been proposed as potential biomarkers. In a study of breast cancer patients, GM3 was found to be an excellent diagnostic marker for the luminal B breast cancer subtype [ 121 ], whereas GM2 has been proposed as a potential biomarker for cholangiocarcinoma [ 122 ]. In children with neuroblastoma, GD2 shed from tumors into the circulation was found to be a highly significant predictor of high‐risk tumors [ 123 ], while the ganglioside profile of patient‐derived melanoma cells was predictive of aggressiveness [ 124 ] and survival [ 125 ].…”

Section: Step 4: Metastasismentioning

confidence: 99%

Sphingolipid metabolism in the development and progression of cancer: one cancer's help is another's hindrance

2021

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Cancer development is a multistep process in which cells must overcome a series of obstacles before they can become fully developed tumors. First, cells must develop the ability to proliferate unchecked. Once this is accomplished, they must be able to invade the neighboring tissue, as well as provide themselves with oxygen and nutrients. Finally, they must acquire the ability to detach from the newly formed mass in order to spread to other tissues, all the while evading an immune system that is primed for their destruction. Furthermore, increased levels of inflammation have been shown to be linked to the development of cancer, with sites of chronic inflammation being a common component of tumorigenic microenvironments. In this Review, we give an overview of the impact of sphingolipid metabolism in cancers, from initiation to metastatic dissemination, as well as discussing immune responses and resistance to treatments. We explore how sphingolipids can either help or hinder the progression of cells from a healthy phenotype to a cancerous one.

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Ganglioside GM2: a potential biomarker for cholangiocarcinoma

Cited by 9 publications

References 29 publications

Inhibition of Ceramide Glycosylation Enhances Cisplatin Sensitivity in Cholangiocarcinoma by Limiting the Activation of the ERK Signaling Pathway

Inhibition of Ceramide Glycosylation Enhances Cisplatin Sensitivity in Cholangiocarcinoma by Limiting the Activation of the ERK Signaling Pathway

Deciphering the Importance of Glycosphingolipids on Cellular and Molecular Mechanisms Associated with Epithelial-to-Mesenchymal Transition in Cancer

Sphingolipid metabolism in the development and progression of cancer: one cancer's help is another's hindrance

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