Galectin-4 functions as a tumor suppressor of human colorectal cancer.
Galectin-4 functions as a tumor suppressor of human colorectal cancer.
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DOI：
10.1002/ijc.25750
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发表时间：
2011-08-15
影响因子：
6.4
通讯作者：
Rao, U. Subrahmanyeswara
中科院分区：
文献类型：
--
作者：
Satelli, Arun;Rao, Prema S.;Thirumala, Seshadri;Rao, U. Subrahmanyeswara
CRC的发展涉及一系列基因改变，蛋白质表达和细胞信号通路改变。在这里，我们确定了分化标志物gal-4在CRC中下调。这项工作的目标是确定gal-4在CRC中的功能。为了这个目标，通过免疫组织化学分析了人结肠活检和含有病理梯度的组织微阵列的gal-4表达。细胞增殖，迁移，运动，强制表达，敲低，细胞周期和凋亡测定用于表征半乳糖醛酸-4的功能。免疫组化证实gal-4在腺瘤中表达显著下调，在浸润性癌中基本不表达。gal-4 -ve细胞中gal-4的强制表达可诱导细胞周期阻滞，并抑制细胞的迁移和运动。此外，gal-4使细胞对CPT诱导的凋亡敏感。Gal-4敲低导致细胞增殖、迁移和运动性增加。发现Gal-4与Wnt信号蛋白相关。最后，gal-4表达导致Wnt信号转导靶基因的下调。这项研究表明，gal-4的损失是一个共同的和具体的事件在CRC。这项研究还表明，半乳糖醛酸-4在体外大肠癌细胞中表现出肿瘤抑制作用。通过其与Wnt信号通路相互作用并下调Wnt信号通路功能的能力，gal-4揭示了Wnt信号通路控制的新维度。因此，gal-4可能被证明是理解CRC生物学的重要分子。
Development of CRC involves a series of genetic alterations with altered expression of proteins and cell signaling pathways. Here, we identified that gal-4, a marker of differentiation, was down-regulated in CRC. The goal of this work was to determine the function of gal-4 in CRC. Toward this goal, the human colon biopsies and tissue microarrays containing a gradient of pathology were analyzed for gal-4 expression by immunohistochemistry. Cell proliferation, migration, motility, forced expression, knockdown, cell cycle and apoptosis assays were used to characterize gal-4 function. Immunohistochemistry identified that gal-4 expression was significantly down-regulated in adenomas and was essentially absent in invasive carcinomas. Forced expression of gal-4 in gal-4 -ve cells induced cell cycle arrest and retarded cell migration and motility. Further, gal-4 sensitized the cells to CPT-induced apoptosis. Gal-4 knockdown resulted in increased cell proliferation, migration and motility. Gal-4 was found to be associated with Wnt signaling proteins. Finally, gal-4 expression led to down-regulation of Wnt signaling target genes. This study demonstrates that loss of gal-4 is a common and specific event in CRC. This study also shows that gal-4 exhibits tumor suppressive effects in colorectal cancer cells in vitro. Through its ability to interact with, and down-regulate the functions of Wnt signaling pathway, gal-4 reveals a new dimension in the control of the Wnt signaling pathway. Thus, gal-4 may prove to be an important molecule in understanding the biology of CRC.
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影响因子：
3.4
作者：
Rao, Prema S.;Satelli, Arun;Zhang, Sheng;Srivastava, Sanjay K.;Srivenugopal, Kalkunte S.;Rao, U. Subrahmanyeswara
通讯作者：
Rao, U. Subrahmanyeswara
影响因子：
3
作者：
Huflejt, ME;Leffler, H
通讯作者：
Leffler, H
DOI：
10.1111/j.1440-1746.2006.04137.x
发表时间：
2006-08-01
影响因子：
4.1
作者：
Ishiguro, Atsushi;Takahata, Takenori;Munakata, Akihiro
通讯作者：
Munakata, Akihiro
影响因子：
11.2
作者：
Kuuselo, Riina;Savinainen, Kimmo;Kallioniemi, Anne
通讯作者：
Kallioniemi, Anne
影响因子：
4.3
作者：
Beerenwinkel, Niko;Antal, Tibor;Dingli, David;Traulsen, Arne;Kinzler, Kenneth W.;Velculescu, Victor E.;Vogelstein, Bert;Nowak, Martin A.
通讯作者：
Nowak, Martin A.