APC
小结
APC是抑癌基因，编码肿瘤抑制蛋白，编码蛋白作为WNT通路的拮抗剂，在WNT/β-catenin信号通路中起负向调节作用，通过调节β-catenin的水平达到抑制肿瘤发生的作用。当APC蛋白活性丧失时，WNT通路异常激活，导致增生进而最终发展成肿瘤。携带APC的胚系致病突的人群患家族性腺瘤性息肉病（FAP）的风险显著升高,FAP患者如果不做预防性手术切除，95%的患者会发展成结直肠癌。同时，约有50%-80%的散发性结直肠癌中检测到APC突变；乳腺癌、胃癌、前列腺癌等肿瘤类型也检测到APC体细胞突变。大多数的APC突变都是功能丧失，并且发生在与β-连环蛋白结合的重要区域。
APC is a negative regulator of the pro-oncogenic WNT/ β-catenin signaling pathway. The main tumor suppressive role of APC is to modulate intracellular levels of β-catenin. APC is an essential member of the destruction complex, which targets cytosolic β-catenin for ubiquitination and degradation. When the activity of APC is lost, there is an aberrant increase in WNT-pathway activation, often leading to hyperplasia and eventually tumor progression. A threshold of APC expression is required to suppress tumor formation, and this level is finely balanced. Germline mutations in the APC gene cause familial adenomatous polyposis (FAP), a disease in which 95% of people progress to develop colorectal cancer. In addition, heritable mutations in APC are responsible for the development of a number of related diseases, including Turcot Syndrome, Gardner Syndrome and Flat Adenoma Syndrome (FAS). APC mutations, much like those seen in FAS, have been observed in 50-80% of sporadic colorectal cancers. Somatic mutations in APC function as tumor-initiating events and are also observed in a number of other human cancers including breast, stomach, and prostate. The majority of APC mutations are loss-of-function and occur in a region important for β-catenin binding.