Expression of Angiogenic Regulators, VEGF and Leptin, Is Regulated by the EGF/PI3K/STAT3 Pathway in Colorectal Cancer Cells
Expression of Angiogenic Regulators, VEGF and Leptin, Is Regulated by the EGF/PI3K/STAT3 Pathway in Colorectal Cancer Cells
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DOI：
10.1002/jcp.21843
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发表时间：
2009-10-01
影响因子：
5.6
通讯作者：
Russo, Antonio
中科院分区：
文献类型：
--
作者：
Cascio, Sandra;Ferla, Rita;Russo, Antonio
瘦素和血管内皮生长因子 (VEGF) 都是生长和血管生成细胞因子，在不同类型的癌症中表达上调，并与肿瘤进展有关。在这里，我们研究了表皮生长因子（EGF）在结肠癌中调节瘦素和 VEGF 表达的分子机制。在结肠癌细胞系 HT-29 中，EGF 诱导信号转导子和转录激活子 3 (STAT3) 与 VEGF 和瘦素启动子内的 STAT3 共有基序结合，并刺激瘦素和 VEGF mRNA 和蛋白质合成。当用磷酸肌醇 3 激酶 (PI3K) 通路抑制剂 LY294002 或针对 STAT3 的小干扰 RNA (siRNA) 处理 HT-29 细胞时，所有这些 EGF 效应均被显着阻断。因此，我们的研究确定 EGF/PI3K/STAT3 信号传导是调节 EGF 响应性结肠癌细胞中 VEGF 和瘦素表达的重要途径。这表明 STAT3 通路可能在抗 EGF 受体药物无效的结肠癌患者中构成有吸引力的药物靶点。 J.细胞。生理学。 221: 189-194, 2009。(C) 2009 Wiley-Liss, Inc.
Both leptin and vascular endothelial growth factor (VEGF) are growth and angiogenic cytokines that are upregulated in different types of cancer and have been implicated in neoplastic progression. Here we investigated the molecular mechanism by which leptin and VEGF expression are regulated in colon cancer by epidermal growth factor (EGF). In colon cancer cell line HT-29, EGF induced the binding of signal transducer and activator transcription 3 (STAT3) to STAT3 consensus motifs within the VEGF and leptin promoters and stimulated leptin and VEGF mRNA and protein synthesis. All these EGF effects were significantly blocked when HT-29 cells were treated with an inhibitor of the phosphoinositide 3-kinase (PI3K) pathway, LY294002, or with small interfering RNA (siRNA) targeting STAT3. Thus, our study identified the EGF/PI3K/STAT3 signaling as an essential pathway regulating VEGF and leptin expression in EGF-responsive colon cancer cells. This suggests that STAT3 pathways might constitute attractive pharmaceutical targets in colon cancer patients where anti-EGF receptor drugs are ineffective. J. Cell. Physiol. 221: 189-194, 2009. (C) 2009 Wiley-Liss, Inc.