Transcription factor PROM induces colon cancer progression by promoting the transition from benign to highly dysplastic phenotype
Transcription factor PROM induces colon cancer progression by promoting the transition from benign to highly dysplastic phenotype
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DOI：
10.1016/j.ccr.2008.02.020
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发表时间：
2008-05-01
期刊：
影响因子：
50.3
通讯作者：
Alitalo, Kari
中科院分区：
文献类型：
--
作者：
Petrova, Tatiana V.;Nykanen, Antti;Alitalo, Kari
果蝇转录因子PROSPERO具有肿瘤抑制作用，已有研究表明，与PROSPERO对应的人类转录因子PROX1在人类癌症中的作用类似。然而，我们在这里表明，PROX1促进结肠腺瘤和结直肠癌进展中的不典型增生。PROX1的表达标志着良性结肠腺瘤向原位癌的转变，它的缺失抑制了人结直肠癌移植瘤和APC(min/+)小鼠肠腺瘤的生长，而它的转基因过表达促进了结直肠癌的发生。此外，在肠道肿瘤中，PROX1是β-连环蛋白/TCF信号通路的直接和剂量依赖的靶点，负责肿瘤的转化。我们的数据强调了癌症发病机制的复杂性，并表明PROX1通过调节细胞极性和黏附参与恶性肿瘤的发展。
The Drosophila transcription factor Prospero functions as a tumor suppressor, and it has been suggested that the human counterpart of Prospero, PROX1, acts similarly in human cancers. However, we show here that PROX1 promotes dysplasia in colonic adenomas and colorectal cancer progression. PROX1 expression marks the transition from benign colon adenoma to carcinoma in situ, and its loss inhibits growth of human colorectal tumor xenografts and intestinal adenomas in Apc (min/+) mice, while its transgenic overexpression promotes colorectal tumorigenesis. Furthermore, in intestinal tumors PROX1 is a direct and dose-dependent target of the beta-catenin/TCF signaling pathway, responsible for the neoplastic transformation. Our data underscore the complexity of cancer pathogenesis and implicate PROX1 in malignant tumor progression through the regulation of cell polarity and adhesion.