Semba S, Yamakawa M, Sasano H
First Department of Pathology, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan. senba.med.id.yamagata-u.ac.jp
Endocr Pathol. 2001 Spring;12(1):1-13. doi: 10.1385/ep:12:1:01.
It has been well-known that the cadherin-catenin complexes bind with intracellular skeleton actin, which result in stabilization of cellular structure and tissue organization. Therefore, the cadherin-catenin family has been considered prerequisite for normal cell function and the preservation of tissue integrity. In human malignancies especially colon cancers, dysfunction and/or decrease of expression of these proteins have been proposed to prevent differentiation of tumors and to increase invasiveness and poor prognosis. However, recent studies also revealed that a member of this superfamily, beta-catenin, may play an important role in Wnt/wingless intracellular signaling pathway. Decreased expression of this protein or somatic mutation of the beta-catenin gene has been also reported in human carcinomas including various endocrine tumors. Mutant beta-catenin is associated with abnormal nuclear accumulation in tumor cells and subsequently to activate other transcription factors such as Tcf/Lef. This activation eventually results in which upregulation of mRNA and protein levels of various cell growth mediators in these endocrine tumors. Therefore, dysfunction of the cadherin-catenin system is considered to be closely correlated with tumorigenesis and development in human endocrine tumors.
众所周知，钙黏蛋白-连环蛋白复合物与细胞内骨架肌动蛋白结合，这导致细胞结构和组织组织的稳定。因此，钙黏蛋白-连环蛋白家族被认为是正常细胞功能和组织完整性维持的先决条件。在人类恶性肿瘤尤其是结肠癌中，这些蛋白质的功能障碍和/或表达降低被认为会阻止肿瘤分化并增加侵袭性和不良预后。然而，最近的研究还表明，这个超家族的一个成员，β-连环蛋白，可能在Wnt/无翅细胞内信号通路中起重要作用。在包括各种内分泌肿瘤在内的人类癌中也报道了该蛋白的表达降低或β-连环蛋白基因的体细胞突变。突变的β-连环蛋白与肿瘤细胞中的异常核积累相关，并随后激活其他转录因子，如Tcf/Lef。这种激活最终导致这些内分泌肿瘤中各种细胞生长介质的mRNA和蛋白质水平上调。因此，钙黏蛋白-连环蛋白系统的功能障碍被认为与人类内分泌肿瘤的发生和发展密切相关。
