Cancer cell metabolic plasticity in migration and metastasis

Mosier, Jenna A.; Schwager, Samantha C.; Boyajian, David A; Reinhart‐King, Cynthia A.

doi:10.1007/s10585-021-10102-1

Cited by 69 publications

(40 citation statements)

References 184 publications

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“…An aspect that has not been attentively considered so far is the metabolic reprogramming occurring in MCC [72]. As reported above, HIF-1α is highly expressed in MCC cells, and, among its downstream targets, there are genes encoding for proteins, such as glucose transporter-1 and monocarboxylate transporters, that initiate the metabolic switching from oxidative phosphorylation to glycolysis characteristic of aggressive tumor cells [135,136]. Toberer et al found that both glucose transporter-1 and monocarboxylate transporter-4 were expressed by MCC cells and that a positive correlation between HIF-1α and glucose transporter-1 expression was present only in MCCP, suggesting a difference in the metabolic signature for the two MCC tumor types [72].…”

Section: Future Perspectivesmentioning

confidence: 99%

Merkel Cell Carcinoma

et al. 2021

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Merkel cell carcinoma (MCC) is a rare and extremely aggressive neuroendocrine carcinoma of the skin, with increasing incidence worldwide. This review intends to propose a comprehensive evaluation of MCC epidemiology, clinical features, pathogenetic mechanisms, diagnosis, and therapies. A section is dedicated to immunological aspects and another to the involvement of angiogenesis and angiogenic growth factors in MCC progression, proposing novel diagnostic and therapeutic approaches. Advanced MCC tumors have been treated with immune checkpoint inhibitors with effective results. Therefore, the state of art of this immunotherapy is also examined, reporting on the most recent clinical trials in the field. We conclude by underlining the achievements in the understanding of MCC pathology and indicating the present needs for effective diagnosis and therapeutic management of the disease.

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Section: Future Perspectivesmentioning

confidence: 99%

Merkel Cell Carcinoma

et al. 2021

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“…Recently, increasing attention has been paid into the exploration of the relationship between cancer cell metabolic plasticity and migration and metastasis ( Mosier et al, 2021 ). Cancer cells with a more invasive and distal metastasis phenotype are found to be strongly correlated with the upregulated expression of peroxisome proliferator-associated receptor gamma and coactivator 1-alpha, which are hallmarks of active mitochondrial biogenesis and oxidative phosphorylation (OXPHOS) ( LeBleu et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Development of an Oxidative Phosphorylation-Related and Immune Microenvironment Prognostic Signature in Uterine Corpus Endometrial Carcinoma

Liu

Chen

Yang

et al. 2021

Front. Cell Dev. Biol.

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Background: As the fourth most common malignant tumors in women, uterine corpus endometrial carcinoma (UCEC) requires novel and reliable biomarkers for prognosis prediction to improve the overall survival. Oxidative phosphorylation (OXPHOS) is found to be strongly correlated with the progression of tumor. Here, we aimed to construct an OXPHOS-related and immune microenvironment prognostic signature to stratify UCEC patients for optimization of treatment strategies.Method: Prognosis-associated OXPHOS-related differentially expressed genes were identified by multivariable Cox regression from TCGA–UCEC cohort. Based on the candidate genes, an OXPHOS-related prognostic signature was constructed by the train set data and verified by the entire set. When integrated with relevant clinical characteristics, a nomogram was also created for clinical application. Through comparison of tumor microenvironment between different risk groups, the underlying mechanism of the model and the inner correlation between immune microenvironment and energy metabolism were further investigated.Results: An OXPHOS-related signature containing ATP5IF1, COX6B1, FOXP3, and NDUFB11 was constructed and had better predictive ability compared with other recently published signatures in UCEC. Patients with lower risk score showed higher immune cell infiltration, higher ESTIMATE score (p = 2.808E−18), lower tumor purity (p = 2.808E−18), higher immunophenoscores (IPSs) (p < 0.05), lower expression of mismatch repair (MMR) proteins (p < 0.05), higher microsatellite instability (MSI), lower expression of markers of N6-methyladenosine (m6A) mRNA methylation regulators, higher tumor mutation burden (TMB) (p = 1.278E−9), and more sensitivity to immune checkpoint blockade (ICB) (p < 0.001) and chemotherapy drugs, thus, possessing improved prognosis.Conclusion: An OXPHOS-related and immune microenvironment prognostic signature classifying EC patients into different risk subsets was constructed in our study, which could be used to predict the prognosis of patients and help to select a specific subset of patients who might benefit from immunotherapy and chemotherapy, thus, improving the overall survival rate of UCEC. These findings may contribute to the discovery of novel and robust biomarkers or target therapy in UCEC and give new insights into the molecular mechanism of tumorigenesis and progression of UCEC.

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“…Reprogramming of carbohydrate metabolism, particularly increased glycolysis, has been recognized as a hallmark of cancer [ 46 ] and plays a key role in cancer progression in different cancers [ 8 , 10 , 47 ], which forms the basis of tumor imaging by positron emission tomography. Targeting glycolytic metabolism has become a potent therapeutic strategy to suppress cancer progression [ 14 , 48 ].…”

Section: Discussionmentioning

confidence: 99%

Characterization of a novel glucocorticoid-resistant human B-cell acute lymphoblastic leukemia cell line, with AMPK, mTOR and fatty acid synthesis pathway inhibition

Zuo

2021

Cancer Cell Int

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Background Acquired glucocorticoid (GC) resistance remains the main obstacle in acute lymphoblastic leukemia (ALL) therapy. The aim of the present study was to establish a novel GC-resistant B-ALL cell line and investigate its biological characteristics. Methods A cell culture technique was used to establish the GC-resistant cell line from the parental cell, NALM-6. Molecular and cellular biological techniques including flow cytometry, MTT assay, western blotting, DNA fingerprinting analysis and whole transcriptome sequencing (WTS) were used to characterize the GC-resistant cell lines. Nude mice were used for xenograft studies. Results The GC-resistant cell line, NALM-6/HDR, was established by culturing NALM-6 cells under hypoxia for 5 weeks with a single dexamethasone (Dex) treatment. We subcloned the NALM-6/HDR cell lines, and got 6 monoclone Dex-resistant cell lines, NALM-6/HDR-C1, C3, C4, C5, C6 and C9 with resistance index (RI) ranging from 20,000–50,000. NALM-6/HDR and its monoclone cell line, NALM-6/HDR-C5, exhibited moderate (RI 5–15) to high resistance (RI > 20) to Ara-c; low or no cross-resistance to L-Asp, VCR, DNR, and MTX (RI < 5). STR analysis confirmed that NALM-6/HDR and NALM-6/H were all derived from NALM-6. All these cells derived from NALM-6 showed similar morphology, growth curves, immunophenotype, chromosomal karyotype and tumorigenicity. WTS analysis revealed that the main metabolic differences between NALM-6 or NALM-6/H (GC-sensitive) and NALM-6/HDR (GC-resistant) were lipid and carbohydrates metabolism. Western blotting analysis showed that NALM-6/HDR cells had a low expression of GR and p-GR. Moreover, AMPK, mTORC1, glycolysis and de novo fatty acid synthesis (FAS) pathway were inhibited in NALM-6/HDR when compared with NALM-6. Conclusions NALM-6/HDR cell line may represent a subtype of B-ALL cells in patients who acquired GC and Ara-c resistance during the treatment. These patients may get little benefit from the available therapy target of AMPK, mTORC1, glycolysis and FAS pathway.

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Cancer cell metabolic plasticity in migration and metastasis

Cited by 69 publications

References 184 publications

Merkel Cell Carcinoma

Merkel Cell Carcinoma

Development of an Oxidative Phosphorylation-Related and Immune Microenvironment Prognostic Signature in Uterine Corpus Endometrial Carcinoma

Characterization of a novel glucocorticoid-resistant human B-cell acute lymphoblastic leukemia cell line, with AMPK, mTOR and fatty acid synthesis pathway inhibition

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