Juanes M Angeles
School of Health and Life Science, Teesside University, Middlesbrough TS1 3BX, UK.
National Horizons Centre, Teesside University, 38 John Dixon Lane, Darlington DL1 1HG, UK.
Cancers (Basel). 2020 Dec 17;12(12):3811. doi: 10.3390/cancers12123811.
Intestinal epithelium architecture is sustained by stem cell division. In principle, stem cells can divide symmetrically to generate two identical copies of themselves or asymmetrically to sustain tissue renewal in a balanced manner. The choice between the two helps preserve stem cell and progeny pools and is crucial for tissue homeostasis. Control of spindle orientation is a prime contributor to the specification of symmetric versus asymmetric cell division. Competition for space within the niche may be another factor limiting the stem cell pool. An integrative view of the multiple links between intracellular and extracellular signals and molecular determinants at play remains a challenge. One outstanding question is the precise molecular roles of the tumour suppressor Adenomatous polyposis coli (APC) for sustaining gut homeostasis through its respective functions as a cytoskeletal hub and a down regulator in Wnt signalling. Here, we review our current understanding of APC inherent activities and partners in order to explore novel avenues by which APC may act as a gatekeeper in colorectal cancer and as a therapeutic target.
肠道上皮结构由干细胞分裂维持。原则上，干细胞可以对称分裂以产生两个相同的自身拷贝，或者不对称分裂以平衡的方式维持组织更新。这两种方式之间的选择有助于维持干细胞和子代细胞库，对组织稳态至关重要。纺锤体方向的控制是决定对称与不对称细胞分裂的主要因素。微环境内的空间竞争可能是限制干细胞库的另一个因素。对细胞内和细胞外信号以及起作用的分子决定因素之间多重联系的综合理解仍然是一个挑战。一个突出的问题是肿瘤抑制因子腺瘤性息肉病大肠杆菌（APC）通过其作为细胞骨架枢纽和Wnt信号通路下调因子的各自功能来维持肠道稳态的确切分子作用。在这里，我们回顾了我们目前对APC固有活性和相关蛋白的理解，以探索APC可能作为结直肠癌的守门人和治疗靶点的新途径。
