Adenomatous polyposis coli (APC) is widely accepted as a tumor suppressor gene highly mutated in colorectal cancers (CRC). Mutation and inactivation of this gene is a key and early event almost uniquely observed in colorectal tumorigenesis. Alterations in the APC gene generate truncated gene products, leading to activation of the Wnt signaling pathway and deregulation of multiple other cellular processes. It has been a mystery why most patients with CRC retain a truncated APC protein, but accumulating evidence suggest that these C terminally truncated APC proteins may have gain of function properties beyond the well-established loss of tumor suppressive function. Here, we will review the evidence for both the loss of function and the gain of function of APC truncations and how together they contribute to CRC initiation and progression.

中文翻译：

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APC在结直肠癌中的多重作用及其治疗意义

腺瘤性息肉病大肠杆菌（APC）被广泛接受为在大肠癌（CRC）中高度突变的抑癌基因。该基因的突变和失活是在大肠肿瘤发生中几乎独特地观察到的关键和早期事件。在改变APC基因产生截短的基因产物，从而导致Wnt信号通路的激活和多个其他细胞过程的失控。为什么大多数CRC患者保留截短的APC蛋白一直是个谜，但是越来越多的证据表明，这些C末端截短的APC蛋白可能具有超出公认的肿瘤抑制功能丧失的功能特性。在这里，我们将回顾APC截短功能丧失和功能获得的证据，以及它们如何共同促进CRC的发生和发展。