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I am not a biologist and I would love to understand what is going on with this pathway.
I went to the description but it's still complicated, and I couldn't follow. Can someone please help me with it? Is this a comprehensive pathway or is it based on specific details? How do i read this pathway?

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  • $\begingroup$ your link doesn't work... $\endgroup$ – MattDMo Apr 1 '15 at 17:08
  • $\begingroup$ @MattDMo thanks I updated it and should work now $\endgroup$ – Learner Apr 1 '15 at 17:09
  • $\begingroup$ Your question is pretty broad. What specifically do you want to know about this pathway? $\endgroup$ – C_Z_ Apr 1 '15 at 17:12
  • $\begingroup$ @CactusWoman my main question is how can we come to such conclusion that a pathway is very important or one is not! how to interpret such pathway shown in the link? and what can I understand from it? to be honest it is very complicated for me to understand it $\endgroup$ – Learner Apr 1 '15 at 17:23
  • $\begingroup$ Please remove the link and make it a stand-alone question. I vote to close as unclear what you are asking. $\endgroup$ – AliceD Apr 1 '15 at 22:30
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So if you're reading the flowchart, understanding the notation of the arrows is important:

  • We have rectangles around the gene products
  • There's a circle, denoted by DNA, noting that the proteins are expressing the product that follows through interaction with DNA
  • The solid line with an arrowhead means there's some sort of interaction
  • The solid line with the blunted or T head means this pathway or interaction has been abrogated somehow
  • The solid line with the slash through it means there's some missing interaction that we don't see
  • The +p means phosphorylation
  • The double solid line to the left is the plasma membrane, whereas the dotted line central to the figure is the nuclear envelope
  • The dotted line means an indirect effect

Source: http://www.genome.jp/kegg/document/help_pathway.html

The pathway is kind of broad but it provides some mechanisms for tumorigenesis from two standpoints: chromosomal instability, and microsatellite instability. The pathways we're seeing promotes the tumor development by upregulating proliferation signals, and downregulating apoptosis pathways. There's bound to be more to it, especially since we see other players involved when we get into cases like metastasis like snail1/2, Met, Src, etc. Below is a survey of apoptotic pathways from Nature, with pro-apoptotic in red, and pro-survival in green:

enter image description here Source: http://www.nature.com/reviews/poster/apoptosis/index.html

Ignoring the therapeutic targeting jargon, you can see that when growth factors bind, the cell generally pushes towards a survival state. When death factors bind or something goes wrong, the cell pushes toward an apoptotic state. Cancers, however, are intrinsically disregulated:

enter image description here

They have methods of overstepping their boundaries as cells, which is what makes them problematic. The general conclusion I'd draw from that KEGG pathway, though, is that many pathways need to be disregulated to end up with colorectal tumors, and the method of disregulation is (a) downmodulated mismatch repair, and (b) chromosomal aberrations due to duplication, etc. Andkeeping in mind the box of oncogenes vs tumor suppressors in the corner: "An important difference between oncogenes and tumor suppressor genes is that oncogenes result from the activation (turning on) of proto-oncogenes, but tumor suppressor genes cause cancer when they are inactivated (turned off)"

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Pathways in biology are very hard to interpret without being an expert in the subject. Here a link to The Standard Graphical Notation for Biological Networks that might help you understanding the notation used.

Pathway are generally based on evidences of links between the players. These links do not require to be found using one particular technique. Those evidences could come from genome-wide association studies (GWAS), RNA-seq, functional assays, receptor based assays, clinical data etc.. just to cite a few.

For example The MAPK pathway was linked to colorectal cancer via gene expression experiments as shown here. The MAPK pathway is known to influence cell proliferation and therefore contributes to colorectal cancer development but if you don't know what the MAPK pathway is doing at first it is hard to comprehend the full picture.

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