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首页> 外文期刊>Cellular Signalling >Proinvasive activity of BMP-7 through SMAD4/src-independent and ERK/Rac JNK-dependent signaling pathways in colon cancer cells
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Proinvasive activity of BMP-7 through SMAD4/src-independent and ERK/Rac JNK-dependent signaling pathways in colon cancer cells

机译：BMP-7通过SMAD4 / src依赖性和ERK / Rac JNK依赖性信号通路在结肠癌细胞中的前侵活性

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Recent data indicate that the Bone Morphogenetic Protein BMP-7 exhibits mucosal protection against experimental colitis in rats, suggesting that this cytokine exerts direct actions in intestinal epithelial cells during inflammatory bowel diseases and other precancerous lesions of the colon. In this study, we investigated the functional expression of BMP-7 and its receptors in normal human colon crypts, aberrant crypt foci (ACF) in sigmoiditis and colorectal tumors, and their derived cancer cell lines. Transcripts encoding BMP-7 receptors type II (BMPRII, ActRII, ActRIIB) and type I (ALK-2) were clearly detected by RT-PCR in several premalignant and carcinoma cell lines. The cytokine was identified by immunohistochemistry in surface epithelial cells and crypts in the normal colon mucosa, ACF in sigmoiditis, sporadic high grade dysplastic adenoma, and in 9 of 16 colon carcinomas (56.2%). In addition, the conditioned medium collected from the adenoma PC/AA/C1 and carcinoma HCT8/S11 and SW48 cell lines in culture contained significant levels of BMP-7 ranging from 0.17 to 0.38 ng/ml. We found that BMP-7 induced scattering and proinvasive responses (EC50= 1 ng/ml) in kidney and colon cancer cell lines through SMAD4 and src-independent pathways and signaling cascades using FAK phosphorylation at Y925 and activation of ERK1/2, Rac1 and JNK. This phosphorylation of FAK on Y925 was also induced by the proinvasive agent EGF. Taken together, our findings suggest that BMP-7 exerts divergent effects in the colon mucosa, one counteracting transient inflammatory situations and the other linked to pejorative functions during chronic ulcerative diseases and the neoplastic
机译：最新数据表明，骨形态发生蛋白BMP-7对大鼠实验性结肠炎具有粘膜保护作用，表明该细胞因子在炎症性肠病和其他结肠癌前病变中在肠上皮细胞中发挥直接作用。在这项研究中，我们调查了BMP-7及其受体在正常人结肠隐窝，乙状结肠炎和结直肠肿瘤中异常隐窝灶（ACF）及其衍生的癌细胞系中的功能表达。通过RT-PCR在几种癌前和癌细胞系中清楚地检测到编码II型BMP-7受体（BMPRII，ActRII，ActRIIB）和I型（ALK-2）的转录物。通过免疫组织化学在正常结肠粘膜的表面上皮细胞和隐窝，乙状结肠炎，散发性高级别增生性腺瘤以及16种结肠癌中的9种（56.2％）中识别出了细胞因子。此外，从培养的腺瘤PC / AA / C1以及癌HCT8 / S11和SW48细胞系中收集的条件培养基中含有的BMP-7水平显着水平介于0.17至0.38 ng / ml之间。我们发现BMP-7通过SMAD4和src无关的途径以及在Y925处使用FAK磷酸化和ERK1 / 2，Rac1和ERK的激活来诱导肾和结肠癌细胞系SMAD4和src独立途径的信号传导和级联反应，从而诱导肾脏和结肠癌细胞系发生散射和侵袭性反应（EC50 = 1 ng / ml）。 JNK。 F925在Y925上的这种磷酸化也由前侵染剂EGF诱导。综上所述，我们的研究结果表明BMP-7在结肠粘膜中发挥不同的作用，一种可以抵消短暂的炎症，而另一种则与慢性溃疡性疾病和赘生物中的脓性功能有关。

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