Colon tumours grow via hidden protein switch
Colorectal cancer cells divide faster when a single inhibitory protein is removed. That protein doesn’t work through a genetic mutation, but through a signaling pathway normally kept under control in healthy gut tissue. The finding may point toward new treatment targets.
The gut lining has a high turnover rate: cells are constantly shed and replaced. That division must be tightly regulated. When the brake is released, cells can begin dividing uncontrollably and a tumor can form. In healthy tissue, the protein SLAP (Src-like adaptor protein) acts as an inhibitory switch on a class of signaling molecules that drive cell division: the Src-family kinases (SFKs).
What SLAP does in the gut
Researchers publishing in eLife showed what happens when that inhibitory protein is removed. The study used a mouse model in which SLAP was specifically deleted from intestinal epithelial cells. The result: cells divided substantially faster, and in a colorectal cancer model, tumor development accelerated. The link to human cancer has not yet been established, but the findings suggest SLAP functions as a tumor suppressor.
The underlying mechanism was notable. When SLAP is absent, the receptor protein EPHB2 accumulates in the cell, activating Src kinases. EPHB2 has previously been linked to tumor development, but the precise chain of cause and effect was unclear. Pharmacological inhibition of EPHB2 in the mouse model largely reversed the excessive cell division. That makes EPHB2 a potential drug target.
A non-genetic mechanism
What distinguishes this finding is that it involves a non-genetic mechanism. Colorectal cancer is typically associated with mutations in well-known genes such as APC or KRAS. Here, the change involves the abundance and activity of a protein, without any alteration to the DNA itself. That is relevant for a subset of tumors in which none of the known mutations are found.
Colorectal cancer becomes more common as people age. Whether the SLAP pathway connects to aging processes has not yet been investigated. The researchers present this as a mechanistic insight, not a clinical application.
Want to research this yourself? Try these search terms: Src-family kinases colorectal tumorigenesis, EPHB2 receptor intestinal epithelium, non-genetic tumor suppression colon cancer