Clinical importance of the cheloid factor

"Cheloid Factor"

Cellular repair may contribute to the recognized increased risk of cancer in areas that have been traumatized.  For example when Radiation was received or a simple surgery was performed.
Intuitively, we assume that stimulation of tissue repair mechanisms and the inflammatory response leads to the increased risk, but to this date there has not sufficient data been collected for indepth checking, and the FAK (focal adhesion Kinases).  Certainly, if the inflammatory and related NF-kB (MAPK), C-jun were the only drivers of the risk of cancer in surgery sites, we believe this risk would be much more prominent that it is, given the frequency of surgical interventions?

Another evidence that the cheloid factor is needed in the cancerization risk is the fact that " a large chinese study showed no benefit in the prevention of gastric cancer with eradication of H.Pylori" (Grothey ).  Meaning that the mere decrease of an Infectious impetus which modulates the NF-kB and the level of cyclins, failed to globally affect the risk of cancer development.  But we know that this Infection needs to be eradicated in patients with demonstrasted gastric Ulcer  disease (Grothey).  Here, we use the presence of an ulcer as a putative presence of disturbance at the FAK! We need funding for such a demonstration!

Conceivably, FAK which involves the Wnt and Notch and their associated involvement of cell polarity (as discussed earlier in depth and breadth) could also play a significant role in the risk for hepatoma. Indeed, the mere presence of Hepatitis B or C does not lead to Hepatoma. It is the evidence of disturbance at regeneration and repair which involves the FAK that leads to Hepatoma.  In fact, in the Western World, Hepatoma is more generated by alcoholic and non alcoholic "trauma" followed by uncontrolled Repair.  The focal adhesion molecules are a significant part of these repair events at the cellular level.  The point is, that with every protein leaving the membrane, with every stimulated receptor detaching from the membrane, with every ions channel stimulated and some tension in these channels, there is potentially an activity going on at the FAK!  and making these events very frequent at the membrane!  Any chronic exposure increases these FAK events further.  The coexistence of any other failure (Mutations at P53, BRCA, p15 or 16, DPC, Rb1 or just at the Glycans ie Heparan sulfate- covering detaching receptors, and at the "switch" molecules (SOS, and others phosphorylation regulators -APC GENE) will exacerbate the risk of neoplastic development.  The interaction with a wild gene will completely establish the neoplastic transformation..

The Melanoma example is just another example of the "cheloid factor" history as solar trauma exposes us to large amounts of FAK solicitations.  Radiation trauma to the marrow adds JAK2 to the danger of FAK sollicitations or influence (proof of concept needed) opening the door to cellular malignancies from the marrow.  Of course, the resulting fibrosis will be Cyclins and Tumor growth factors (TNF) related detaching more receptors and exposing FAK or Focal Adhesions membrane molecules!

Under this prism, Neoplasia seems to be linked not only to specific genes that must Mutate, but more to the global number of Focal adhesion Molecules exposed.   The fact that anti-inflammatory agents which decrease the number of detaching receptors induced by inflammatory cytokines, reducing FAK exposure and globally reducing Neoplastic risk, adds more credence to this theory! (Proof of concept)   Antioxidant by reducing free radicals and resulting sollicitation of proteins attached to the membranes, will do just the same!  Indeed, the very notion of Biomarkers followed in the serum,  marks protein rates and FAK exposure!

(IF ANYTHING, THIS THEORY MUST BE PURSUED ! AND CPRIT CAN HELP!)