Molecular Definition of a Novel Human Galectin Which Is Immunogenic in Patients with Hodgkin's Disease

Türeci, Özlem; Schmitt, Holger; Fadle, Natalie; Pfreundschuh, Michael; Şahin, Uğur

doi:10.1074/jbc.272.10.6416

Cited by 221 publications

(143 citation statements)

References 35 publications

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“…Galectin-7, which is highly inducible by p53 (23) and normally expressed in stratified epithelia, is down-regulated in squamous cell carcinomas (36). Galectin-8 is overexpressed in prostate cancer (37), and galectin-9 is overexpressed in Hodgkin's lymphomas (38,39). Whether the altered expression of galec-tins contributes to the neoplastic transformation or is a consequence of the transformation awaits elucidation.…”

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confidence: 99%

Cell Cycle Regulation by Galectin-12, a New Member of the Galectin Superfamily

Yang

Hsu

et al. 2001

Journal of Biological Chemistry

127

129

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Galectins are a family of ␤-galactoside-binding animal lectins with conserved carbohydrate recognition domains (CRDs). Here we report the identification and characterization of a new galectin, galectin-12, which contains two domains that are homologous to the galectin CRD. The N-terminal domain contains all of the sequence elements predicted to form the two ␤-sheets found in other galectins, as well as conserved carbohydrate-interacting residues. The C-terminal domain shows considerable divergence from the consensus sequence, and many of these conserved residues are not present. Nevertheless, the protein has lactose binding activity, most likely due to the contribution of the Nterminal domain. The mRNA for galectin-12 contains features coding for proteins with growth-regulatory functions. These include start codons in a context that are suboptimal for translation initiation and AU-rich motifs in the 3-untranslated region, which are known to confer instability to mRNA. Galectin-12 mRNA is sparingly expressed or undetectable in many tissues and cell lines tested, but it is up-regulated in cells synchronized at the G 1 phase or the G 1 /S boundary of the cell cycle. Ectopic expression of galectin-12 in cancer cells causes cell cycle arrest at the G 1 phase and cell growth suppression. We conclude that galectin-12 is a novel regulator of cellular homeostasis.

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confidence: 99%

Cell Cycle Regulation by Galectin-12, a New Member of the Galectin Superfamily

Yang

Hsu

et al. 2001

Journal of Biological Chemistry

127

129

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“…10 Recent studies suggested that galectin-9 is a modulator of immune functions; it induces chemotaxis of eosinophils 11 and apoptosis of thymocytes, suggesting a possible role in the process of negative selection occurring during T-cell development. 12 With the objective of finding newer agents for the treatment of ATL, the present study was designed to investigate the antitumor potential of galectin-9 on HTLV-I-infected T-cell lines and primary ATL cells in vitro and in vivo, and the possible mechanisms involved in such antitumor activities.…”

mentioning

confidence: 99%

Retracted: A modified version of galectin‐9 suppresses cell growth and induces apoptosis of human T‐cell leukemia virus type I‐infected T‐cell lines

Okudaira

Hirashima

Ishikawa

et al. 2007

Intl Journal of Cancer

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ATL is a fatal malignancy of T lymphocytes caused by HTLV-I infection and remains incurable. Galectins are a family of animal lectins that function both extracellularly (by interacting with cell surface and extracellular matrix glycoproteins and glycolipids) and intracellularly (by interacting with cytoplasmic and nuclear proteins) to modulate signaling pathways. We found that protease-resistant galectin-9 by modification of its linker peptide, hG9NC(null), prevented cell growth of HTLV-I-infected T-cell lines and primary ATL cells. The suppression of cell growth was inhibited by lactose, but not by sucrose, indicating that b-galactoside binding is essential for hG9NC(null)-induced cell growth suppression. hG9NC(null) induced cell cycle arrest by reducing the expression of cyclin D1, cyclin D2, cyclin B1, Cdk1, Cdk4, Cdk6, Cdc25C and c-Myc, and apoptosis by reducing the expression of XIAP, c-IAP2 and survivin. Most of these genes are regulated by NF-jB, which plays a critical role in oncogenesis by HTLV-I. hG9NC(null) suppressed IjBa phosphorylation, resulting in suppression of NF-jB. Most importantly, treatment with hG9NC(null) (6.7 mg/kg injected intraperitoneally every day) reduced tumor formation from an HTLV-I-infected T-cell line when these cells were inoculated subcutaneously into SCID mice. Our results suggest that hG9NC(null) could be a suitable agent for the management of ATL. ' 2007 Wiley-Liss, Inc.Key words: galectin-9; HTLV-I; ATL; NF-kB; apoptosis ATL is a unique malignancy of mature CD4-positive T cells caused by HTLV-I. 1-3 ATL is subclassified into 4 subtypes: acute, lymphoma, chronic and smoldering. In the relatively indolent smoldering and chronic types, the median survival time is more than 2 years. However, at present, there is no accepted curative therapy for ATL and the condition often progresses to death with a median survival time of 13 months in aggressive ATL. 4 Chemotherapies that are specifically known to be active against other lymphoid malignancies are ineffective for treating aggressive forms of ATL. Death is usually due to severe infection or hypercalcemia. Therefore, the establishment of new therapeutic strategies for ATL is very important.Galectins are a family of soluble b-galactoside binding animal lectins. To date, 14 members of the galectin family have been identified. Each member exhibits diverse biological functions and many of them appear to function in cellular homeostasis through regulation of cell adhesion, cell proliferation, cell death and chemoattraction. [5][6][7][8][9] The members can be classified into 3 subtypes according to their structures. The prototype (galectin-1, -2, -7, -10 and -13) and chimera type (galectin-3) galectins have a single CRD and they usually form a noncovalent homodimer resulting in homobifunctional sugar binding activity. Tandem-repeat type galectins (galectin-4, -8, -9 and -12) have two CRDs, which generally show different sugar binding specificities, joined by a linker peptide. This heterobifunctional property makes them capable of cros...

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“…Galectin-9 has been detected extracellularly and intracellularly, and the expression of the protein is widely distributed in tissues (27,28). Indeed, the available results suggest that galectin-9 expression is frequently altered when comparing tumor tissue with normal tissue (29).…”

Section: Discussionmentioning

confidence: 99%

miR-455-5p functions as a potential oncogene by targeting galectin-9 in colon cancer

et al. 2017

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Abstract.Although there is evidence that galectin-9 is a critical factor in health and disease, the upstream regulatory microRNA (miRNA or miR) of the protein remains poorly defined. miR-455-5p is characterized as a tumor-associated miRNA in cancer research. However, the actual role of miR-455-5p with respect to inhibiting or promoting tumorigenesis in colon cancer is unclear. The present study aimed to investigate the expression, role and target regulation association of galectin-9 and miR-455-5p in colon cancer. Western blot analysis and reverse transcription-quantitative polymerase chain reaction were used for the detection of the expression levels of galectin-9 and miRNAs. Cell Counting kit-8 test was used for the evaluation of cell proliferation, while flow cytometry was used for cell apoptosis analysis. A potential interaction between galectin-9 and miR-455-5p was predicted by target prediction programs and confirmed by luciferase assay and transfection with miRNA mimics. The present study revealed that elevated expression of galectin-9 and miR-455-5p in colon cancer was associated with HT29 cell proliferation and apoptosis. Furthermore, the present study demonstrated that miR-455-5p reduced galectin-9 expression by directly targeting its 3'-untranslated region. These data suggest that miR-455-5p functions as a potential oncogene in colon cancer by targeting galectin-9.

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Molecular Definition of a Novel Human Galectin Which Is Immunogenic in Patients with Hodgkin's Disease

Cited by 221 publications

References 35 publications

Cell Cycle Regulation by Galectin-12, a New Member of the Galectin Superfamily

Cell Cycle Regulation by Galectin-12, a New Member of the Galectin Superfamily

Retracted: A modified version of galectin‐9 suppresses cell growth and induces apoptosis of human T‐cell leukemia virus type I‐infected T‐cell lines

miR-455-5p functions as a potential oncogene by targeting galectin-9 in colon cancer

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