Lee Nikki P, Poon Ronnie T P, Shek Felix H, Ng Irene O L, Luk John M
Department of Surgery, The University of Hong Kong, Hong Kong.
Biochim Biophys Acta. 2010 Dec;1806(2):138-45. doi: 10.1016/j.bbcan.2010.05.002. Epub 2010 May 24.
Cadherin is an important cell adhesion molecule that plays paramount roles in organ development and the maintenance of tissue integrity. Dysregulation of cadherin expression is often associated with disease pathology including tissue dysplasia, tumor formation, and metastasis. Cadherin-17 (CDH17), belonging to a subclass of 7D-cadherin superfamily, is present in fetal liver and gastrointestinal tract during embryogenesis, but the gene becomes silenced in healthy adult liver and stomach tissues. It functions as a peptide transporter and a cell adhesion molecule to maintain tissue integrity in epithelia. However, recent findings from our group and others have reported aberrant expression of CDH17 in major gastrointestinal malignancies including hepatocellular carcinoma (HCC), stomach and colorectal cancers, and its clinical association with tumor metastasis and advanced tumor stages. Furthermore, alternative splice isoforms and genetic polymorphisms of CDH17 gene have been identified in HCC and linked to an increased risk of HCC. CDH17 is an attractive target for HCC therapy. Targeting CDH17 in HCC can inhibit tumor growth and inactivate Wnt signaling pathway in concomitance with activation of tumor suppressor genes. Further investigation on CDH17-mediated oncogenic signaling and cognate molecular mechanisms would shed light on new targeting therapy on HCC and potentially other gastrointestinal malignancies.
钙黏蛋白是一种重要的细胞黏附分子，在器官发育和维持组织完整性方面发挥着至关重要的作用。钙黏蛋白表达失调通常与包括组织发育异常、肿瘤形成和转移在内的疾病病理相关。钙黏蛋白-17（CDH17）属于7D-钙黏蛋白超家族的一个亚类，在胚胎发生过程中存在于胎儿肝脏和胃肠道中，但该基因在健康的成人肝脏和胃组织中会沉默。它作为一种肽转运体和细胞黏附分子，维持上皮组织的完整性。然而，我们团队和其他团队最近的研究结果报告了CDH17在包括肝细胞癌（HCC）、胃癌和结直肠癌在内的主要胃肠道恶性肿瘤中的异常表达，以及它与肿瘤转移和肿瘤晚期的临床关联。此外，已在HCC中鉴定出CDH17基因的可变剪接异构体和基因多态性，并与HCC风险增加相关。CDH17是HCC治疗的一个有吸引力的靶点。在HCC中靶向CDH17可以抑制肿瘤生长，并使Wnt信号通路失活，同时激活肿瘤抑制基因。对CDH17介导的致癌信号和相关分子机制的进一步研究将为HCC以及潜在的其他胃肠道恶性肿瘤的新靶向治疗提供线索。
