Intrinsic 5-lipoxygenase activity regulates migration and adherence of mantle cell lymphoma cells

Xia, Chuanyou; Sadeghi, Laia; Strååt, Klas; Merrien, Magali; Wright, Andrew N.; Sander, Birgitta; Xu, Dawei; Österborg, Anders; Björkholm, Magnus; Claesson, Hans-Erik

doi:10.1016/j.prostaglandins.2021.106575

Cited by 8 publications

(3 citation statements)

References 36 publications

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“…Xia et al. (2021) have shown that CRISPR‐Cas9‐mediated knockdown and pharmacologic inhibition of the ALOX5 gene inhibits cell migration and adherence in the MCL cell line. In addition, alcohol‐induced splenic cell loss and ratio imbalance will lead to changes in the signaling network of chemokines, cytokines, and adhesion molecules produced by the spleen cells, thus affecting the normal recruitment and migration of cells, resulting in abnormal organization of splenic compartments (Hermida et al., 2018).…”

Section: Discussionmentioning

confidence: 99%

“…Figure 6C showed the individual z-score of each molecule, NKBIA, ALOX5, and PRF1 showed the highest z-score ≈1. ALOX5 and its activating protein FLAP are expressed in most of the B cells.ALOX5 pathway plays a crucial role in the migration and adherence of the cells and contributes to the pathologic characteristics of B-cell lymphoma(Mahshid et al, 2009) Xia et al (2021). have shown that CRISPR-Cas9-mediated knockdown and pharmacologic inhibition of the ALOX5 gene inhibits cell migration and adherence in the MCL cell line.…”

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confidence: 99%

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The mechanisms underlying alcohol‐induced decreased splenic size: A network meta‐analysis study

Liu,

Bishir,

Hodgkinson

et al. 2023

Alcohol: Clinical and Experimental Research

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BackgroundOrgan weight change is widely accepted as a measure of toxicologic pathology. We and other groups have shown that excessive alcohol exposure leads to decreased spleen weight in rodents. This study explores the mechanisms underlying alcohol‐induced splenic injury through a network meta‐analysis.MethodsQIAGEN Ingenuity Pathway Analysis (IPA) and Mammalian Phenotype (MP) Ontology were used to identify alcohol‐related molecules associated with the small spleen phenotype. Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and IPA bioinformatics tools were then used to analyze the biologic processes and enriched signaling pathways engaging these molecules. In addition, the “downstream effects analysis” algorithm was used to quantify alcohol's effects.ResultsIPA identified 623 molecules affected by alcohol and a Venn diagram revealed that 26 of these molecules overlapped with those associated with the MP Ontology of small spleen. The 26 molecules are TGFB1, CASP8, MTOR, ESR1, CXCR4, CAMK4, NFKBIA, DRD2, BCL2, FAS, PEBP1, TRAF2, ATM, IGHM, EDNRB, MDM2, GLRA1, PRF1, TLR7, IFNG, ALOX5, FOXO1, IL15, APOE, IKBKG, and RORA. Some of the 26 molecules were also associated with the MP Ontology of abnormal white pulp and red pulp morphology of the spleen, abnormal splenic cell ratio, decreased splenocyte number, abnormal spleen physiology, increased splenocyte apoptosis, and reduced splenocyte proliferation. STRING and IPA “Core Analysis” showed that these molecules were mainly involved in pathways related to cell apoptosis, proliferation, migration, and immune responses. IPA's “Molecular Activity Predictor” tool showed that concurrent effects of activation and inhibition of these molecules led to decreased spleen size by modulating apoptosis, proliferation, and migration of splenocytes.ConclusionsOur network meta‐analysis revealed that excessive alcohol exposure can damage the spleen through a variety of molecular mechanisms, thereby affecting immune function and human health. We found that alcohol‐mediated splenic atrophy is largely mediated by increased apoptosis signaling, migration of cells, and inhibition of splenocyte proliferation.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

The mechanisms underlying alcohol‐induced decreased splenic size: A network meta‐analysis study

Liu,

Bishir,

Hodgkinson

et al. 2023

Alcohol: Clinical and Experimental Research

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“…Whereas 5-LOX and 12-LOX have been identified with angiogenetic and protumorigenic activities, 15-LOX exerts both protumorigenic and antitumorigenic effects [234]. As a key enzyme in metabolizing arachidonic acid to leukotrienes, 5-LOX is highly expressed in epithelial cancers as well as lymphomas [235,236]. Inhibiting approaches targeting 5-LOX were used to inhibit tumorigenesis [226,237].…”

Section: Lipoxygenase (Lox) Signalingmentioning

confidence: 99%

Targeting inflammation as cancer therapy

Wang,

Chen,

et al. 2024

J Hematol Oncol

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Inflammation has accompanied human beings since the emergence of wounds and infections. In the past decades, numerous efforts have been undertaken to explore the potential role of inflammation in cancer, from tumor development, invasion, and metastasis to the resistance of tumors to treatment. Inflammation-targeted agents not only demonstrate the potential to suppress cancer development, but also to improve the efficacy of other therapeutic modalities. In this review, we describe the highly dynamic and complex inflammatory tumor microenvironment, with discussion on key inflammation mediators in cancer including inflammatory cells, inflammatory cytokines, and their downstream intracellular pathways. In addition, we especially address the role of inflammation in cancer development and highlight the action mechanisms of inflammation-targeted therapies in antitumor response. Finally, we summarize the results from both preclinical and clinical studies up to date to illustrate the translation potential of inflammation-targeted therapies.

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