Myelopoietic Efficacy of Orlistat in Murine Hosts Bearing T Cell Lymphoma: Implication in Macrophage Differentiation and Activation

Kant, Shri; Kumar, Ajay; Singh, Sukh Mahendra

doi:10.1371/journal.pone.0082396

Cited by 9 publications

(8 citation statements)

References 67 publications

(95 reference statements)

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“…FASN is considered an oncogene in carcinogenesis and has emerged as a potential therapeutic target for lymphoma ( 37 , 38 ). In the present study, substantial evidence is presented regarding the association of FASN expression with DLBCL.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of fatty acid synthase in MYC and BCL‑2 double‑expressor lymphoma

Zhong

Liu

et al. 2021

Oncol Lett

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Diffuse large B-cell lymphoma (DLBCL) is the most common and heterogeneous lymphoid malignancy. The subtype with MYC and BCL-2 double-expressor lymphoma (DEL) was defined by its aggressive nature and poor survival outcome. Therefore, the development of effective therapies for the DEL subtype is imperative. Fatty acid synthase (FASN) activity is associated with altered lipid metabolism and aberrant protein translation in DLBCL. However, the inter-regulation of these key processes is not fully determined in DEL. In the present study, the clinical and biological impact of FASN was investigated in the DEL subtype. Initially, FASN expression levels were analyzed from a patient cohort and the data indicated that the highest FASN expression was noted in DEL tissues compared with that noted in the DLBCL and reactive lymphoid hyperplasia tissues. Patients with DEL with combined high-FASN expression indicated poorer EFS outcomes than the rest of the patients. In vitro data indicated that FASN was overexpressed in SU-DHL-2 and U2932 cells. Silencing FASN decreased cell growth and promoted cell apoptosis by modulating the pERK/BCL-2 signaling pathway. In conclusion, the present study indicated that FASN was overexpressed in DEL and that its expression was associated with poor survival outcomes. Furthermore, the data demonstrated that FASN regulated the biological function via the pERK/BCL-2 signaling pathway. FASN serves a critical role in the progression of DEL and its expression may be associated with the development to a more aggressive phenotype of DLBCL. Therefore, it may be considered a potential therapeutic target for DLBCL.

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Section: Discussionmentioning

confidence: 99%

Upregulation of fatty acid synthase in MYC and BCL‑2 double‑expressor lymphoma

Zhong

Liu

et al. 2021

Oncol Lett

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“…As for another group of GO terms, there are multiple immune responses associated GO terms, including positive regulation of macrophage differentiation and cellular response to interferon-alpha. According to recent publications, macrophage differentiation ( Kant et al, 2013 ; Arlt et al, 2020 ) and interferon-alpha ( Hermine et al, 2002 ) associated immune responses have both been reported to be associated with the pathogenesis of lymphoma.…”

Section: Discussionmentioning

confidence: 99%

A Random Walk-Based Method to Identify Candidate Genes Associated With Lymphoma

et al. 2021

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Lymphoma is a serious type of cancer, especially for adolescents and elder adults, although this malignancy is quite rare compared with other types of cancer. The cause of this malignancy remains ambiguous. Genetic factor is deemed to be highly associated with the initiation and progression of lymphoma, and several genes have been related to this disease. Determining the pathogeny of lymphoma by identifying the related genes is important. In this study, we presented a random walk-based method to infer the novel lymphoma-associated genes. From the reported 1,458 lymphoma-associated genes and protein–protein interaction network, raw candidate genes were mined by using the random walk with restart algorithm. The determined raw genes were further filtered by using three screening tests (i.e., permutation, linkage, and enrichment tests). These tests could control false-positive genes and screen out essential candidate genes with strong linkages to validate the lymphoma-associated genes. A total of 108 inferred genes were obtained. Analytical results indicated that some inferred genes, such as RAC3, TEC, IRAK2/3/4, PRKCE, SMAD3, BLK, TXK, PRKCQ, were associated with the initiation and progression of lymphoma.

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“…The activity of FASN in cancer cells has staid acquaintances with the regulation of antitumor immune response. The elevated level of FASN, observed in T-cell tumors, correlated with the decreased level of antitumor response by tumor-infiltrating macrophages ( 184 ). Moreover, inhibition of FASN through small molecule inhibitors withdraws the suppression of hematopoietic differentiation of bone marrow cells ( 184 ).…”

Section: Immunosuppression and Immune Escapementioning

confidence: 99%

Orchestral role of lipid metabolic reprogramming in T-cell malignancy

Mehta

Ratre

Soni³

et al. 2023

Front. Oncol.

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The immune function of normal T cells partially depends on the maneuvering of lipid metabolism through various stages and subsets. Interestingly, T-cell malignancies also reprogram their lipid metabolism to fulfill bioenergetic demand for rapid division. The rewiring of lipid metabolism in T-cell malignancies not only provides survival benefits but also contributes to their stemness, invasion, metastasis, and angiogenesis. Owing to distinctive lipid metabolic programming in T-cell cancer, quantitative, qualitative, and spatial enrichment of specific lipid molecules occur. The formation of lipid rafts rich in cholesterol confers physical strength and sustains survival signals. The accumulation of lipids through de novo synthesis and uptake of free lipids contribute to the bioenergetic reserve required for robust demand during migration and metastasis. Lipid storage in cells leads to the formation of specialized structures known as lipid droplets. The inimitable changes in fatty acid synthesis (FAS) and fatty acid oxidation (FAO) are in dynamic balance in T-cell malignancies. FAO fuels the molecular pumps causing chemoresistance, while FAS offers structural and signaling lipids for rapid division. Lipid metabolism in T-cell cancer provides molecules having immunosuppressive abilities. Moreover, the distinctive composition of membrane lipids has implications for immune evasion by malignant cells of T-cell origin. Lipid droplets and lipid rafts are contributors to maintaining hallmarks of cancer in malignancies of T cells. In preclinical settings, molecular targeting of lipid metabolism in T-cell cancer potentiates the antitumor immunity and chemotherapeutic response. Thus, the direct and adjunct benefit of lipid metabolic targeting is expected to improve the clinical management of T-cell malignancies.

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Myelopoietic Efficacy of Orlistat in Murine Hosts Bearing T Cell Lymphoma: Implication in Macrophage Differentiation and Activation

Cited by 9 publications

References 67 publications

Upregulation of fatty acid synthase in MYC and BCL‑2 double‑expressor lymphoma

Upregulation of fatty acid synthase in MYC and BCL‑2 double‑expressor lymphoma

A Random Walk-Based Method to Identify Candidate Genes Associated With Lymphoma

Orchestral role of lipid metabolic reprogramming in T-cell malignancy

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