Galectin-9 exhibits anti-myeloma activity through JNK and p38 MAP kinase pathways

Kobayashi, Tsutomu; Kuroda, Junya; Ashihara, Eishi; Oomizu, Souichi; Terui, Yasuhito; Taniyama, Akiko; Adachi, Satoko; Takagi, Tomohisa; Yamamoto, Masakuni; Sasaki, Nana; Horiike, Shigeo; Hatake, Kiyohiko; Yamauchi, Akira; Hirashima, Mitsuomi

doi:10.1038/leu.2010.25

Cited by 82 publications

(97 citation statements)

References 36 publications

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“…In addition, one study supports the hypothesis that galectin-9 is involved in several aspects of tumor progression (30). Galectin-9 also induces the apoptosis of various cell types, including human melanoma, T cell and leukemia cell lines (13,31,32). The present study explored the expression and potential role of galectin-9 in colon cancer, and noticed that galectin-9 was significantly downregulated in colon cancer tissue compared with corresponding adjacent tissue.…”

Section: Discussionsupporting

confidence: 49%

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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Section: Discussionsupporting

confidence: 49%

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

et al. 2017

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“…Kobayashi et al (2010) confirmed that Gal-9 exhibits anti-myeloma activity through JNK and p38 MAP kinase pathways. In our present study, we found that Gal-9 suppression reduced apoptosis in HepG2 cells at about 30% (data not shown).…”

Section: Discussionmentioning

confidence: 61%

Galectin-9 Acts as a Prognostic Factor with Antimetastatic Potential in Hepatocellular Carcinoma

Zhang¹,

Dong²,

Chen³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Considerable research has been conducted concerning galectin-9 and carcinomas, but little information is available about any relation with the hepatocellular carcinoma. In this study, we employed a small interfering RNA (siRNA) targeting galectin-9 to down-regulate the expression in HepG2 cells. As a result, after galectin-9 expression was reduced, cell aggregation was suppressed, while other behaviour such as the proliferation, adhesion and invasion to ECM, cell-endothelial adhesion and transendothelial invasion of the cells were markedly enhanced. When tumors of 200 patients with hepatocellular carcinoma were tested for galectin-9 expression by immunohistochemistry, binding levels demonstrated intimate correlations with the histopathologic grade, lymph node metastasis, vascular invasion and intrahepatic metastasis (P<0.05). Moreover, survival analysis indicated that patients with galectin-9 expression had much longer survival time than those with negative lesions, and the Log-rank test indicated that this difference was statistical significant (P<0.0001). The Cox proportional hazards model suggested that negative galectin-9 expression in hepatocellular carcinoma represented a significant risk factor for patient survival. We propose that galectin-9 might be a new prognostic factor with antimetastatic potential in patients with hepatocellular carcinoma.

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“…Regarding the mechanism underlying Gal-9-induced cell growth inhibition in various cancers, Gal-9 induces cancer cell death via an apoptotic signaling pathway (11)(12)(13). This apoptotic signaling in multiple myeloma was caspase-dependent and was induced by the activation of the MAP kinases JNK and p38 (22,29). Alternatively, Gal-9 induced apoptosis in chronic myelogenous leukemia by inducing Noxa (12).…”

Section: Discussionmentioning

confidence: 99%

Galectin-9: An anticancer molecule for gallbladder carcinoma

Tadokoro

Morishita

Fujihara

et al. 2016

International Journal of Oncology

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Abstract. Gallbladder cancer (GBC) is the most common and aggressive type of biliary tract cancer. There are various histological types of GBC, and the vast majority of GBC cases are adenocarcinomas. Squamous and adenosquamous carcinomas are rare GBC subtypes that are traditionally considered to be more aggressive and to be associated with a poorer prognosis than adenocarcinoma. Galectin-9 (Gal-9), a tandem-repeattype galectin, has been reported to induce apoptosis-mediated elimination of various cancers, including hepatocellular carcinoma, cholangiocarcinoma, and hematologic malignancies. Therefore, we investigated the antitumor effects of Gal-9 on GBC in vitro and in vivo. In our in vitro experiments, Gal-9 suppressed cell proliferation in various GBC cell lines but not in the OCUG-1 cell line, which represents a poorly differentiated type of adenosquamous carcinoma. Gal-9 induced the apoptosis of Gal-9-sensitive GBC cells by increasing the levels of caspase-cleaved keratin 18 and phosphorylated p53. However, Gal-9 did not affect the expression of various cell cycle-related proteins. In addition, Gal-9 suppressed tumor growth by implanted human GBC cells in a xenograft model. Furthermore, Gal-9 induced the phosphorylation of the Ephrin type-B receptor, and the microRNA (miRNA) expression profile was markedly altered by Gal-9. Based on these results, various miRNAs might contribute to the suppression of tumor growth. Our data reveal that Gal-9 suppresses the growth of GBC, possibly by inducing apoptosis and altering miRNA expression. Thus, Gal-9 might serve as a therapeutic agent for the treatment of GBC.

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Galectin-9 exhibits anti-myeloma activity through JNK and p38 MAP kinase pathways

Cited by 82 publications

References 36 publications

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

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

Galectin-9 Acts as a Prognostic Factor with Antimetastatic Potential in Hepatocellular Carcinoma

Galectin-9: An anticancer molecule for gallbladder carcinoma

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