Sialic Acid Metabolism: A Key Player in Breast Cancer Metastasis Revealed by Metabolomics

Teoh, Shao Thing; Ogrodzinski, Martin P.; Ross, Christina R.; Hunter, Kent W.; Lunt, Sophia Y.

doi:10.3389/fonc.2018.00174

Cited by 75 publications

(65 citation statements)

References 74 publications

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“…So far, our results indicate that loss of sialic acids might actually be detrimental in CRC and thereby contradict other studies investigating the role of tumor sialylation on the anti‐tumor immune response . To translate our findings to human CRC patients, we analyzed CMAS gene expression in a human colorectal cancer cohort (GSE39582) in relation to disease progression and survival.…”

Section: Resultscontrasting

confidence: 62%

“…The different mouse strains, with their different predisposition toward T helper 2 (Th2) and Th1 responses, as well as the different tumor model used, may have impacted the outcome of the respective studies. Discrepancies due to tumor type‐specific effects is further supported by the cohort data presented in both studies (Fig. a ).…”

Section: Discussionsupporting

confidence: 62%

“…However, the choice of the target gene cannot fully explain the observed discrepancies. Teoh et al . recently showed decreased lung metastasis upon CMAS gene knock out in a highly metastatic mammary cell line injected in BALB/c mice.…”

Section: Discussionmentioning

confidence: 99%

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Disruption of sialic acid metabolism drives tumor growth by augmenting CD8⁺ T cell apoptosis

Cornelissen

Blanas

Horst

et al. 2019

Intl Journal of Cancer

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Sialylated glycan structures are known for their immunomodulatory capacities and their contribution to tumor immune evasion. However, the role of aberrant sialylation in colorectal cancer and the consequences of complete tumor desialylation on anti‐tumor immunity remain unstudied. Here, we report that CRISPR/Cas9‐mediated knock out of the CMAS gene, encoding a key enzyme in the sialylation pathway, in the mouse colorectal cancer MC38 cell line completely abrogated cell surface expression of sialic acids (MC38‐Sianull) and, unexpectedly, significantly increased in vivo tumor growth compared to the control MC38‐MOCK cells. This enhanced tumor growth of MC38‐Sianull cells could be attributed to decreased CD8+ T cell frequencies in the tumor microenvironment only, as immune cell frequencies in tumor‐draining lymph nodes remained unaffected. In addition, MC38‐Sianull cells were able to induce CD8+ T cell apoptosis in an antigen‐independent manner. Moreover, low CMAS gene expression correlated with reduced recurrence‐free survival in a human colorectal cancer cohort, supporting the clinical relevance of our work. Together, these results demonstrate for the first time a detrimental effect of complete tumor desialylation on colorectal cancer tumor growth, which greatly impacts the design of novel cancer therapeutics aimed at altering the tumor glycosylation profile.

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Section: Resultscontrasting

confidence: 62%

Section: Discussionsupporting

confidence: 62%

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Disruption of sialic acid metabolism drives tumor growth by augmenting CD8⁺ T cell apoptosis

Cornelissen

Blanas

Horst

et al. 2019

Intl Journal of Cancer

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“…Generally, tumor cells increase the uptake of glucose, the raw material for sialic acid synthesis. It was reported that sialic acid metabolism was upregulated in highly metastatic breast tumors, while knocking out CMAS gene, a key node in sialic acid metabolism, inhibited the synthesis of the activated form of sialic acid and decreased the formation of lung metastases in vivo [32]. On the other hand, the aberrant expression of sialyltransferases and sialidases accelerated and sustained sialylation status on glycoconjugates.…”

Section: Functions Of Sialic Acids In Tumor Biologymentioning

confidence: 99%

Biological Functions and Analytical Strategies of Sialic Acids in Tumor

Zhou

Yang

Guan

2020

Cells

131

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Sialic acids, a subset of nine carbon acidic sugars, often exist as the terminal sugars of glycans on either glycoproteins or glycolipids on the cell surface. Sialic acids play important roles in many physiological and pathological processes via carbohydrate-protein interactions, including cell–cell communication, bacterial and viral infections. In particular, hypersialylation in tumors, as well as their roles in tumor growth and metastasis, have been widely described. Recent studies have indicated that the aberrant sialylation is a vital way for tumor cells to escape immune surveillance and keep malignance. In this article, we outline the present state of knowledge on the metabolic pathway of human sialic acids, the function of hypersialylation in tumors, as well as the recent labeling and analytical techniques for sialic acids. It is expected to offer a brief introduction of sialic acid metabolism and provide advanced analytical strategies in sialic acid studies.

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“…CMAS, which is in the sialic acid pathway, has a key role in breast cancer and is significantly associated with decreased breast cancer patient survival. Also, low CMAS gene expression is correlated with reduced recurrencefree survival in a human colorectal cancer cohort [27,28]. XCL2 expression increases with the degree of malignancy of lung cancer, indicating that it could be an important target in gene therapy for lung cancer [29].…”

Section: Discussionmentioning

confidence: 98%

Gene expression dynamic analysis reveals co-activation of Sonic Hedgehog and epidermal growth factor followed by dynamic silencing

et al. 2020

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Aberrant activation of the Sonic Hedgehog (SHH) gene is observed in various cancers. Previous studies have shown a "cross-talk" effect between the canonical Hedgehog signaling pathway and the Epidermal Growth Factor (EGF) pathway when SHHis active in the presence of EGF. However, the precise mechanism of the cross-talk effect on the entire gene population has not been investigated. Here, we re-analyzed publicly available data to study how SHH and EGF cooperate to affect the dynamic activity of the gene population. We used genome dynamic analysis to explore the expression profiles under different conditions in a human medulloblastoma cell line. Ordinary differential equations, equipped with solid statistical and computational tools, were exploited to extract the information hidden in the dynamic behavior of the gene population. Our results revealed that EGF stimulation plays a dominant role, overshadowing most of the SHH effects. We also identified cross-talk genes that exhibited expression profiles dissimilar to that seen under SHH or EGF stimulation alone. These unique cross-talk patterns were validated in a cell culture model. These cross-talk genes identified here may serve as valuable markers to study or test for EGF co-stimulatory effects in an SHH+ environment. Furthermore, these cross-talk genes may play roles in cancer progression, thus they may be further explored as cancer treatment targets.

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Sialic Acid Metabolism: A Key Player in Breast Cancer Metastasis Revealed by Metabolomics

Cited by 75 publications

References 74 publications

Disruption of sialic acid metabolism drives tumor growth by augmenting CD8⁺ T cell apoptosis

Disruption of sialic acid metabolism drives tumor growth by augmenting CD8⁺ T cell apoptosis

Biological Functions and Analytical Strategies of Sialic Acids in Tumor

Gene expression dynamic analysis reveals co-activation of Sonic Hedgehog and epidermal growth factor followed by dynamic silencing

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Sialic Acid Metabolism: A Key Player in Breast Cancer Metastasis Revealed by Metabolomics

Cited by 75 publications

References 74 publications

Disruption of sialic acid metabolism drives tumor growth by augmenting CD8+ T cell apoptosis

Disruption of sialic acid metabolism drives tumor growth by augmenting CD8+ T cell apoptosis

Biological Functions and Analytical Strategies of Sialic Acids in Tumor

Gene expression dynamic analysis reveals co-activation of Sonic Hedgehog and epidermal growth factor followed by dynamic silencing

Contact Info

Product

Resources

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Disruption of sialic acid metabolism drives tumor growth by augmenting CD8⁺ T cell apoptosis

Disruption of sialic acid metabolism drives tumor growth by augmenting CD8⁺ T cell apoptosis