Molecular basis of aberrant cellular pathways in gastrointestinal cancer and its application to diagnosis and treatment

本研究从新的生物学角度阐明了致癌β-catenin信号通路在结直肠癌（CRC）中的独特病理作用。包括编码区决定簇结合蛋白（CRD-BP）作为β-catenin/Tcf复合物的一个新的转录靶点，通过介导Wnt和hedgehog通路之间的相互作用在CRC中的病理作用;以及细胞极性丧失、细胞粘附障碍和β-catenin致癌激活在CRC肿瘤发生中的因果关系。我们还证实了GSK 3 β抑制剂对胃肠道癌细胞侵袭和耐药的治疗作用，并揭示了以GSK 3 β为靶点治疗胃肠道癌的分子基础。

This study clarified the distinct pathologic roles of oncogenic β-catenin signaling in colorectal cancer (CRC) from the new biological points of view. They include putative pathologic role for coding region determinant-binding protein (CRD-BP), a novel transcriptional target of β-catenin/Tcfcomplex, in promoting CRC by mediating interaction between Wnt and hedgehog pathways; and the causative relationship among loss of cell polarity, cell adhesion disorder and oncogenic activation of β-catenin in CRC tumorigenesis. We also demonstrated the therapeutic effects of GSK3β inhibition against invasion of gastrointestinal (GI) cancer cells and their resistance to therapies, and uncovered the molecular basis for the novel traetment of GI cancer by targeting GSK3β.