好久没有继续我的学习/写作/科普大业了，这个positive feedback loop是非常powerful的。
这一期的主题，Apc - Wnt - CRC
这也是我今后的研究主题。
先抛出问题：
- Wnt pathway的组成成分有哪些，都控制了哪些重要的细胞功能？
- 正常情况下，Apc是如何与Wnt互作的？
- ApcKO后4-8 day，为何Wnt没有被激活了，什么东西出现了代替了Apc？
基本科普：
- Wnt proteins are secreted morphogens【所以在cellchat里就是个Secreted Signaling的类别】，ligand一般是Wnt.x，而受体则是FZD.x + LRP.x，FZDx的别名就是Frizzled。
- β-catenin的基因名是CTNNB1，这是一个转录因子coactivator，acts as a coactivator for transcription factors of the TCF/LEF family, leading to activate Wnt responsive genes
- TCF/LEF, The TCF/LEF family (T cell factor/lymphoid enhancer factor family) is a group of genes that encode transcription factors which bind to DNA through a SOX-like high mobility group domain. They are involved in the Wnt signaling pathway, particularly during embryonic [2] and stem-cell development,[3] but also had been found to play a role in cancer[4] and diabetes.[5] TCF/LEF factors recruit the coactivator beta-catenin to enhancer elements of genes they target.
- KEGG 的 Wnt signaling pathway - Homo sapiens (human)
其他的非典型Wnt通路
- The term non-canonical pathway refers to a group of wnt-dependent signalling pathways which do not lead to the cytoplasmic stabilization of soluble β-catenin.
- Two of these pathways have been well characterized: the planar cell polarity (PCP) and the wnt-Calcium pathway.
Wnt通路核心元件
KEGG精细描绘 - https://www.genome.jp/pathway/hsa04310
重点阐述：
- DVL是第一站的重要中介，一旦ligand+receptor激活，DVL就可以抑制GSK3β的磷酸化活性，β-catenin就自由了，进入细胞核联合CBP等coactivator来配合TCF/LEF家族的TF来激活Wnt通路的靶基因；
- ligand+receptor未激活时，GSK3β的磷酸化活性就无人（DVL）抑制，其联合AXIN和APC即可将β-catenin磷酸化+泛素化降解，缺乏β-catenin这个核心的coactivator，TCF/LEF家族的TF就无法运转；【CK1a也是降解中的一个重要元件】